TY  - JOUR
AU  - Đuran, Boris
AU  - Tatić, Zoran
AU  - Perunović, Neda
AU  - Pejčić, Nataša
AU  - Vuković, Jovana
AU  - Petković-Ćurčin, Aleksandra
AU  - Vojvodić, Danilo
AU  - Rakić, Mia
PY  - 2023
UR  - https://www.mdpi.com/1660-4601/20/1/477
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9819861
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5403
AB  - Peri-implant diseases are an emerging public health problem, and it's considered that limitations of standard diagnostics play the role herein. The study objective was the estimation of pathological bone resorption at clinical and biological level in patients with peri-implant mucositis (PIM) and peri-implantitis (PI) before and 6 months after standard treatment and to compare them with healthy controls (HC). The split-mouth interventional study included 60 patients affected with PIM or PI. Patients that also presented at least one more HC were enrolled in the study and underwent standard non-surgical and surgical treatment, respectively. Standard clinical parameters and soluble levels of RANKL were measured in peri-implant crevicular fluid baseline and 6 months following treatment. Clinical parameters and RANKL significantly decreased following treatment in PIM and PI. However, bleeding on probing and probing depth remained significantly increased when compared to HC. RANKL answered requests for biomarker of peri-implant diseases, its baseline levels were significantly increased in PIM and PI, they decreased following treatment and reached HC in peri-implantitis, while in PIM RANKL remained significantly increased. Presence of pathological bone resorption in patients lacked its clinical signs, and respective persistence following treatment suggest the need for biomarker-supported diagnosis for timely diagnosis of peri-implantitis and appropriate orientation of respective management strategies.
PB  - Basel: MDPI
T2  - International Journal of Environmental Research and Public Health
T1  - Underdiagnosis in Background of Emerging Public Health Challenges Related to Peri-Implant Diseases: An Interventional Split-Mouth Study
IS  - 1
VL  - 20
DO  - 10.3390/ijerph20010477
SP  - 477
ER  - 

@article{
author = "Đuran, Boris and Tatić, Zoran and Perunović, Neda and Pejčić, Nataša and Vuković, Jovana and Petković-Ćurčin, Aleksandra and Vojvodić, Danilo and Rakić, Mia",
year = "2023",
abstract = "Peri-implant diseases are an emerging public health problem, and it's considered that limitations of standard diagnostics play the role herein. The study objective was the estimation of pathological bone resorption at clinical and biological level in patients with peri-implant mucositis (PIM) and peri-implantitis (PI) before and 6 months after standard treatment and to compare them with healthy controls (HC). The split-mouth interventional study included 60 patients affected with PIM or PI. Patients that also presented at least one more HC were enrolled in the study and underwent standard non-surgical and surgical treatment, respectively. Standard clinical parameters and soluble levels of RANKL were measured in peri-implant crevicular fluid baseline and 6 months following treatment. Clinical parameters and RANKL significantly decreased following treatment in PIM and PI. However, bleeding on probing and probing depth remained significantly increased when compared to HC. RANKL answered requests for biomarker of peri-implant diseases, its baseline levels were significantly increased in PIM and PI, they decreased following treatment and reached HC in peri-implantitis, while in PIM RANKL remained significantly increased. Presence of pathological bone resorption in patients lacked its clinical signs, and respective persistence following treatment suggest the need for biomarker-supported diagnosis for timely diagnosis of peri-implantitis and appropriate orientation of respective management strategies.",
publisher = "Basel: MDPI",
journal = "International Journal of Environmental Research and Public Health",
title = "Underdiagnosis in Background of Emerging Public Health Challenges Related to Peri-Implant Diseases: An Interventional Split-Mouth Study",
number = "1",
volume = "20",
doi = "10.3390/ijerph20010477",
pages = "477"
}

Đuran, B., Tatić, Z., Perunović, N., Pejčić, N., Vuković, J., Petković-Ćurčin, A., Vojvodić, D.,& Rakić, M.. (2023). Underdiagnosis in Background of Emerging Public Health Challenges Related to Peri-Implant Diseases: An Interventional Split-Mouth Study. in International Journal of Environmental Research and Public Health
Basel: MDPI., 20(1), 477.
https://doi.org/10.3390/ijerph20010477

Đuran B, Tatić Z, Perunović N, Pejčić N, Vuković J, Petković-Ćurčin A, Vojvodić D, Rakić M. Underdiagnosis in Background of Emerging Public Health Challenges Related to Peri-Implant Diseases: An Interventional Split-Mouth Study. in International Journal of Environmental Research and Public Health. 2023;20(1):477.
doi:10.3390/ijerph20010477 .

Đuran, Boris, Tatić, Zoran, Perunović, Neda, Pejčić, Nataša, Vuković, Jovana, Petković-Ćurčin, Aleksandra, Vojvodić, Danilo, Rakić, Mia, "Underdiagnosis in Background of Emerging Public Health Challenges Related to Peri-Implant Diseases: An Interventional Split-Mouth Study" in International Journal of Environmental Research and Public Health, 20, no. 1 (2023):477,
https://doi.org/10.3390/ijerph20010477 . .

TY  - JOUR
AU  - Avramović, Vladimir
AU  - Frederiksen, Simona Denise
AU  - Brkić, Marjana
AU  - Tarailo-Graovac, Maja
PY  - 2021
UR  - https://humgenomics.biomedcentral.com/articles/10.1186/s40246-021-00371-y
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8670043
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4756
AB  - BACKGROUND Genetic variation databases provide invaluable information on the presence and frequency of genetic variants in the 'untargeted' human population, aggregated with the primary goal to facilitate the interpretation of clinically important variants. The presence of somatic variants in such databases can affect variant assessment in undiagnosed rare disease (RD) patients. Previously, the impact of somatic mosaicism was only considered in relation to two Mendelian disease-associated genes. Here, we expand the analyses to identify additional mosaicism-prone genes in blood-derived reference population databases. RESULTS To identify additional mosaicism-prone genes relevant to RDs, we focused on known/previously established ClinVar pathogenic and likely pathogenic single-nucleotide variants, residing in genes associated with early onset, severe autosomal dominant diseases. We asked whether any of these variants are present in a higher-than-expected frequency in the reference population databases and whether there is evidence of somatic origin (i.e., allelic imbalance) rather than germline heterozygosity (~ half of the reads supporting alternative allele). The mosaicism-prone genes identified were further categorized according to the processes they are involved in. Beyond the previously reported ASXL1 and DNMT3A, we identified 7 additional autosomal dominant RD-associated genes with known pathogenic single-nucleotide variants present in the reference population databases and good evidence of allelic imbalance: BRAF, CBL, FGFR3, IDH2, KRAS, PTPN11 and SETBP1. From this group of 9 genes, the majority (n = 7) was important for hematopoiesis. In addition, 4 of these genes were involved in cell proliferation. Further assessment of the known 156 hematopoietic genes led to identification of 48 genes (21 not yet associated with RDs) with at least some evidence of mosaicism detectable in reference population databases. CONCLUSIONS These results stress the importance of considering genes involved in hematopoiesis and cell proliferation when interpreting the presence and frequency of genetic variants in blood-derived reference population databases, both public and private. This is especially important when considering new variants of uncertain significance in known hematopoietic/cell proliferation RD genes and future novel gene-disease associations involving this class of genes.
PB  - London: BioMed Central Ltd
T2  - Human Genomics
T1  - Driving mosaicism: somatic variants in reference population databases and effect on variant interpretation in rare genetic disease.
IS  - 1
VL  - 15
DO  - 10.1186/s40246-021-00371-y
SP  - 71
ER  - 

@article{
author = "Avramović, Vladimir and Frederiksen, Simona Denise and Brkić, Marjana and Tarailo-Graovac, Maja",
year = "2021",
abstract = "BACKGROUND Genetic variation databases provide invaluable information on the presence and frequency of genetic variants in the 'untargeted' human population, aggregated with the primary goal to facilitate the interpretation of clinically important variants. The presence of somatic variants in such databases can affect variant assessment in undiagnosed rare disease (RD) patients. Previously, the impact of somatic mosaicism was only considered in relation to two Mendelian disease-associated genes. Here, we expand the analyses to identify additional mosaicism-prone genes in blood-derived reference population databases. RESULTS To identify additional mosaicism-prone genes relevant to RDs, we focused on known/previously established ClinVar pathogenic and likely pathogenic single-nucleotide variants, residing in genes associated with early onset, severe autosomal dominant diseases. We asked whether any of these variants are present in a higher-than-expected frequency in the reference population databases and whether there is evidence of somatic origin (i.e., allelic imbalance) rather than germline heterozygosity (~ half of the reads supporting alternative allele). The mosaicism-prone genes identified were further categorized according to the processes they are involved in. Beyond the previously reported ASXL1 and DNMT3A, we identified 7 additional autosomal dominant RD-associated genes with known pathogenic single-nucleotide variants present in the reference population databases and good evidence of allelic imbalance: BRAF, CBL, FGFR3, IDH2, KRAS, PTPN11 and SETBP1. From this group of 9 genes, the majority (n = 7) was important for hematopoiesis. In addition, 4 of these genes were involved in cell proliferation. Further assessment of the known 156 hematopoietic genes led to identification of 48 genes (21 not yet associated with RDs) with at least some evidence of mosaicism detectable in reference population databases. CONCLUSIONS These results stress the importance of considering genes involved in hematopoiesis and cell proliferation when interpreting the presence and frequency of genetic variants in blood-derived reference population databases, both public and private. This is especially important when considering new variants of uncertain significance in known hematopoietic/cell proliferation RD genes and future novel gene-disease associations involving this class of genes.",
publisher = "London: BioMed Central Ltd",
journal = "Human Genomics",
title = "Driving mosaicism: somatic variants in reference population databases and effect on variant interpretation in rare genetic disease.",
number = "1",
volume = "15",
doi = "10.1186/s40246-021-00371-y",
pages = "71"
}

Avramović, V., Frederiksen, S. D., Brkić, M.,& Tarailo-Graovac, M.. (2021). Driving mosaicism: somatic variants in reference population databases and effect on variant interpretation in rare genetic disease.. in Human Genomics
London: BioMed Central Ltd., 15(1), 71.
https://doi.org/10.1186/s40246-021-00371-y

Avramović V, Frederiksen SD, Brkić M, Tarailo-Graovac M. Driving mosaicism: somatic variants in reference population databases and effect on variant interpretation in rare genetic disease.. in Human Genomics. 2021;15(1):71.
doi:10.1186/s40246-021-00371-y .

Avramović, Vladimir, Frederiksen, Simona Denise, Brkić, Marjana, Tarailo-Graovac, Maja, "Driving mosaicism: somatic variants in reference population databases and effect on variant interpretation in rare genetic disease." in Human Genomics, 15, no. 1 (2021):71,
https://doi.org/10.1186/s40246-021-00371-y . .

TY  - JOUR
AU  - Mladenović, Aleksandra
AU  - Lončarević Vasiljković, Nataša
AU  - Gonos, Efstathios S.
PY  - 2021
UR  - https://pubmed.ncbi.nlm.nih.gov/32242468/
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4208
AB  - Significance: It is well established that lifestyle and dietary habits have a tremendous impact on life span, the rate of aging, and the onset/progression of age-related diseases. Specifically, dietary restriction (DR) and other healthy dietary patterns are usually accompanied by physical activity and differ from Western diet that is rich in fat and sugars. Moreover, as the generation of reactive oxidative species is the major causative factor of aging, while DR could modify the level of oxidative stress, it has been proposed that DR increases both survival and longevity. Recent Advances: Despite the documented links between DR, aging, and oxidative stress, many issues remain to be addressed. For instance, the free radical theory of aging is under "re-evaluation,"while DR as a golden standard for prolonging life span and ameliorating the effects of aging is also under debate. Critical Issues: This review article pays special attention to highlight the link between DR and oxidative stress in both aging and age-related diseases. We discuss in particular DR's capability to counteract the consequences of oxidative stress and the molecular mechanisms involved in these processes. Future Directions: Although DR is undoubtedly beneficial, several considerations must be taken into account when designing the best dietary intervention. Use of intermittent fasting, daily food reduction, or DR mimetics? Future research should unravel the pros and cons of all these processes. Antioxid. Redox Signal. 34, 421-438.
PB  - Mary Ann Liebert Inc.
T2  - Antioxidants and Redox Signaling
T1  - Dietary Restriction and Oxidative Stress: Friends or Enemies?
IS  - 5
VL  - 34
DO  - 10.1089/ars.2019.7959
SP  - 421
EP  - 438
ER  - 

@article{
author = "Mladenović, Aleksandra and Lončarević Vasiljković, Nataša and Gonos, Efstathios S.",
year = "2021",
abstract = "Significance: It is well established that lifestyle and dietary habits have a tremendous impact on life span, the rate of aging, and the onset/progression of age-related diseases. Specifically, dietary restriction (DR) and other healthy dietary patterns are usually accompanied by physical activity and differ from Western diet that is rich in fat and sugars. Moreover, as the generation of reactive oxidative species is the major causative factor of aging, while DR could modify the level of oxidative stress, it has been proposed that DR increases both survival and longevity. Recent Advances: Despite the documented links between DR, aging, and oxidative stress, many issues remain to be addressed. For instance, the free radical theory of aging is under "re-evaluation,"while DR as a golden standard for prolonging life span and ameliorating the effects of aging is also under debate. Critical Issues: This review article pays special attention to highlight the link between DR and oxidative stress in both aging and age-related diseases. We discuss in particular DR's capability to counteract the consequences of oxidative stress and the molecular mechanisms involved in these processes. Future Directions: Although DR is undoubtedly beneficial, several considerations must be taken into account when designing the best dietary intervention. Use of intermittent fasting, daily food reduction, or DR mimetics? Future research should unravel the pros and cons of all these processes. Antioxid. Redox Signal. 34, 421-438.",
publisher = "Mary Ann Liebert Inc.",
journal = "Antioxidants and Redox Signaling",
title = "Dietary Restriction and Oxidative Stress: Friends or Enemies?",
number = "5",
volume = "34",
doi = "10.1089/ars.2019.7959",
pages = "421-438"
}

Mladenović, A., Lončarević Vasiljković, N.,& Gonos, E. S.. (2021). Dietary Restriction and Oxidative Stress: Friends or Enemies?. in Antioxidants and Redox Signaling
Mary Ann Liebert Inc.., 34(5), 421-438.
https://doi.org/10.1089/ars.2019.7959

Mladenović A, Lončarević Vasiljković N, Gonos ES. Dietary Restriction and Oxidative Stress: Friends or Enemies?. in Antioxidants and Redox Signaling. 2021;34(5):421-438.
doi:10.1089/ars.2019.7959 .

Mladenović, Aleksandra, Lončarević Vasiljković, Nataša, Gonos, Efstathios S., "Dietary Restriction and Oxidative Stress: Friends or Enemies?" in Antioxidants and Redox Signaling, 34, no. 5 (2021):421-438,
https://doi.org/10.1089/ars.2019.7959 . .

TY  - JOUR
AU  - Taso, Ervin
AU  - Rakić, Mia
AU  - Stefanović, Vladimir
AU  - Petković-Ćurčin, Aleksandra
AU  - Stanojević, Ivan
AU  - Đukić, Mirjana
AU  - Struillou, Xavier
AU  - Vojvodić, Danilo
AU  - Banović, Tatjana
AU  - Kanjevac, Tatjana
PY  - 2020
UR  - https://content.sciendo.com/doi/10.2478/sjecr-2019-0015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4167
AB  - Profiling of biomarkers of physiological process represents an integrative part in optimisation of diagnostic markers in order to adjust the diagnostic ranges to the potential effects of the local factors such occlusal forces in case of periodontal tissues. The objective of this study was estimation of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, TNFα and IFNγ concentrations in gingival crevicular fluid samples (GCF) between different groups of teeth. Two hundred fifty-nine systemically healthy non-smokers having at least one vital tooth without restorations, with healthy periodontal tissues, were clinically examined and the GCF sample was retrieved. The cytokine levels were estimated using flow cytometry and compared between central incisors (CI), lateral incisors, canines, first premolars, second premo-lars, first molars and second molars. Cytokine profiles varied between different groups of teeth with tendency of increase in pro-inflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context. Cytokine profiles varied between different groups of teeth with tendency of increase in pro-inflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context.
AB  - Profilisanje biomarkera fiziološkog procesa predstavlja integrativni deo optimalizacije dijagnostičkih markera, kako bi se dijagnostički rasponi prilagodili potencijalnim uticajima lokalnih faktora poput okluzijskih sila u slučaju parodontalnih tkiva. Cilj ove studije bila je procena koncentracija IL-1b, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL- 22, TNFα i IFNγ u uzorcima gingivalne tečnosti (GT) kod različitih grupa zuba. Klinički je pregledano dvesta pedeset devet sistemski zdravih nepušača sa najmanje jednim vitalnim zubom bez restauracija, sa zdravim parodontalnim tkivima, i uzet je GT uzorak. Nivoi citokina procenjeni su protočnom citometrijom i upoređeni između centralnih sekutića (CS), bočnih sekutića, očnjaka, prvih i drugih premolara, kao i prvih i drugih kutnjaka. Profil citokina varirao je između različitih grupa zuba sa tendencijom povećanja pro-upalnih citokina od prednjih zuba do kutnjaka. Molari se mogu smatrati zubima sa prirodnom predispozicijom za bržu resorpciju kosti, dok bi podešavanje dijagnostičkog raspona parodontalnih biomarkera za prednje ili zadnje zube trebalo razmotriti unutar dijagnostičkog konteksta.
PB  - Walter de Gruyter GmbH
T2  - Serbian Journal of Experimental and Clinical Research
T1  - Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth
T1  - Varijacija profila citokina u gingivalnoj zglobnoj tečnosti između različitih grupa parodontalno zdravih zuba
IS  - 4
VL  - 21
DO  - 10.2478/sjecr-2019-0015
SP  - 333
EP  - 341
ER  - 

@article{
author = "Taso, Ervin and Rakić, Mia and Stefanović, Vladimir and Petković-Ćurčin, Aleksandra and Stanojević, Ivan and Đukić, Mirjana and Struillou, Xavier and Vojvodić, Danilo and Banović, Tatjana and Kanjevac, Tatjana",
year = "2020",
abstract = "Profiling of biomarkers of physiological process represents an integrative part in optimisation of diagnostic markers in order to adjust the diagnostic ranges to the potential effects of the local factors such occlusal forces in case of periodontal tissues. The objective of this study was estimation of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, TNFα and IFNγ concentrations in gingival crevicular fluid samples (GCF) between different groups of teeth. Two hundred fifty-nine systemically healthy non-smokers having at least one vital tooth without restorations, with healthy periodontal tissues, were clinically examined and the GCF sample was retrieved. The cytokine levels were estimated using flow cytometry and compared between central incisors (CI), lateral incisors, canines, first premolars, second premo-lars, first molars and second molars. Cytokine profiles varied between different groups of teeth with tendency of increase in pro-inflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context. Cytokine profiles varied between different groups of teeth with tendency of increase in pro-inflammatory cytokines from anterior teeth toward molars. Molars might be considered teeth with natural predisposition for faster bone resorption while the adjustment of diagnostic range of periodontal biomarkers for anterior or posterior teeth should be considered within diagnostic context., Profilisanje biomarkera fiziološkog procesa predstavlja integrativni deo optimalizacije dijagnostičkih markera, kako bi se dijagnostički rasponi prilagodili potencijalnim uticajima lokalnih faktora poput okluzijskih sila u slučaju parodontalnih tkiva. Cilj ove studije bila je procena koncentracija IL-1b, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL- 22, TNFα i IFNγ u uzorcima gingivalne tečnosti (GT) kod različitih grupa zuba. Klinički je pregledano dvesta pedeset devet sistemski zdravih nepušača sa najmanje jednim vitalnim zubom bez restauracija, sa zdravim parodontalnim tkivima, i uzet je GT uzorak. Nivoi citokina procenjeni su protočnom citometrijom i upoređeni između centralnih sekutića (CS), bočnih sekutića, očnjaka, prvih i drugih premolara, kao i prvih i drugih kutnjaka. Profil citokina varirao je između različitih grupa zuba sa tendencijom povećanja pro-upalnih citokina od prednjih zuba do kutnjaka. Molari se mogu smatrati zubima sa prirodnom predispozicijom za bržu resorpciju kosti, dok bi podešavanje dijagnostičkog raspona parodontalnih biomarkera za prednje ili zadnje zube trebalo razmotriti unutar dijagnostičkog konteksta.",
publisher = "Walter de Gruyter GmbH",
journal = "Serbian Journal of Experimental and Clinical Research",
title = "Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth, Varijacija profila citokina u gingivalnoj zglobnoj tečnosti između različitih grupa parodontalno zdravih zuba",
number = "4",
volume = "21",
doi = "10.2478/sjecr-2019-0015",
pages = "333-341"
}

Taso, E., Rakić, M., Stefanović, V., Petković-Ćurčin, A., Stanojević, I., Đukić, M., Struillou, X., Vojvodić, D., Banović, T.,& Kanjevac, T.. (2020). Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth. in Serbian Journal of Experimental and Clinical Research
Walter de Gruyter GmbH., 21(4), 333-341.
https://doi.org/10.2478/sjecr-2019-0015

Taso E, Rakić M, Stefanović V, Petković-Ćurčin A, Stanojević I, Đukić M, Struillou X, Vojvodić D, Banović T, Kanjevac T. Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth. in Serbian Journal of Experimental and Clinical Research. 2020;21(4):333-341.
doi:10.2478/sjecr-2019-0015 .

Taso, Ervin, Rakić, Mia, Stefanović, Vladimir, Petković-Ćurčin, Aleksandra, Stanojević, Ivan, Đukić, Mirjana, Struillou, Xavier, Vojvodić, Danilo, Banović, Tatjana, Kanjevac, Tatjana, "Variation of the Cytokine Profiles in Gingival Crevicular Fluid Between Different Groups of Periodontally Healthy Teeth" in Serbian Journal of Experimental and Clinical Research, 21, no. 4 (2020):333-341,
https://doi.org/10.2478/sjecr-2019-0015 . .

TY  - JOUR
AU  - Petković, Branka
AU  - Kesić, Srđan
AU  - Pešić, Vesna
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3642
AB  - Substance-use disorder represents a frequently hidden non-communicable chronic disease. Patients with intravenous drug addiction are at high risk of direct exposure to a variety of viral infections and are considered to be the largest subpopulation infected with the hepatitis C virus. Ribavirin is a synthetic nucleoside analog that has been used as an integral component of hepatitis C therapy. However, ribavirin medication is quite often associated with pronounced psychiatric adverse effects. It is not well understood to what extent ribavirin per se contributes to changes in drug-related neurobehavioral disturbances, especially in the case of psychostimulant drugs such as amphetamine. It is now well-known that repeated amphetamine usage produces psychosis in humans and behavioral sensitization in animals. On the other hand, ribavirin has an affinity for adenosine A1 receptors that antagonistically modulate the activity of dopamine D1 receptors, which play a critical role in the development of behavioral sensitization. This review will focus on the current knowledge of neurochemical/neurobiological changes that exist in the psychostimulant drug-addicted brain itself and the antipsychotic-like efficiency of adenosine agonists. Particular attention will be paid to the potential side effects of ribavirin therapy, and the opportunities and challenges related to its application in already existing psychostimulant-use disorder.
PB  - Bentham Science Publishers Ltd.
T2  - Current Pharmaceutical Design
T1  - Critical View on the Usage of Ribavirin in Already Existing Psychostimulant-Use Disorder
IS  - 4
VL  - 26
DO  - 10.2174/1381612826666200115094642
SP  - 466
EP  - 484
ER  - 

@article{
author = "Petković, Branka and Kesić, Srđan and Pešić, Vesna",
year = "2020",
abstract = "Substance-use disorder represents a frequently hidden non-communicable chronic disease. Patients with intravenous drug addiction are at high risk of direct exposure to a variety of viral infections and are considered to be the largest subpopulation infected with the hepatitis C virus. Ribavirin is a synthetic nucleoside analog that has been used as an integral component of hepatitis C therapy. However, ribavirin medication is quite often associated with pronounced psychiatric adverse effects. It is not well understood to what extent ribavirin per se contributes to changes in drug-related neurobehavioral disturbances, especially in the case of psychostimulant drugs such as amphetamine. It is now well-known that repeated amphetamine usage produces psychosis in humans and behavioral sensitization in animals. On the other hand, ribavirin has an affinity for adenosine A1 receptors that antagonistically modulate the activity of dopamine D1 receptors, which play a critical role in the development of behavioral sensitization. This review will focus on the current knowledge of neurochemical/neurobiological changes that exist in the psychostimulant drug-addicted brain itself and the antipsychotic-like efficiency of adenosine agonists. Particular attention will be paid to the potential side effects of ribavirin therapy, and the opportunities and challenges related to its application in already existing psychostimulant-use disorder.",
publisher = "Bentham Science Publishers Ltd.",
journal = "Current Pharmaceutical Design",
title = "Critical View on the Usage of Ribavirin in Already Existing Psychostimulant-Use Disorder",
number = "4",
volume = "26",
doi = "10.2174/1381612826666200115094642",
pages = "466-484"
}

Petković, B., Kesić, S.,& Pešić, V.. (2020). Critical View on the Usage of Ribavirin in Already Existing Psychostimulant-Use Disorder. in Current Pharmaceutical Design
Bentham Science Publishers Ltd.., 26(4), 466-484.
https://doi.org/10.2174/1381612826666200115094642

Petković B, Kesić S, Pešić V. Critical View on the Usage of Ribavirin in Already Existing Psychostimulant-Use Disorder. in Current Pharmaceutical Design. 2020;26(4):466-484.
doi:10.2174/1381612826666200115094642 .

Petković, Branka, Kesić, Srđan, Pešić, Vesna, "Critical View on the Usage of Ribavirin in Already Existing Psychostimulant-Use Disorder" in Current Pharmaceutical Design, 26, no. 4 (2020):466-484,
https://doi.org/10.2174/1381612826666200115094642 . .

TY  - JOUR
AU  - Petković, Branka
AU  - Kesić, Srđan
AU  - Ristić, Slavica
AU  - Pavković, Željko
AU  - Podgorac, Jelena
AU  - Stojadinović, Gordana
AU  - Pešić, Vesna
PY  - 2020
UR  - https://www.eurekaselect.com/180519/article
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32213154
UR  - https://radar.ibiss.bg.ac.rs/123456789/3879
AB  - BACKGROUND Psychotic states related to psychostimulant misuse in patients with hepatitis C virus infection may complicate acceptance and reaction to antiviral treatment. This observation equally applies to widely used ribavirin therapy. OBJECTIVE We examined psychomotor and body weight gain response to low ribavirin doses after cessation of intermittent amphetamine treatment in adult rats to assess its role in neurobehavioral outcome during psychostimulant withdrawal. METHOD The model of amphetamine-induced (1.5 mg/kg/day, i.p., 7 consecutive days) motor sensitization and affected body weight gain was established in adult male Wistar rats. Then, additional cohort of amphetamine-sensitized rats was subjected to saline (0.9% NaCl; 1 mL/kg/day; i.p.) or ribavirin (10, 20 and 30 mg/kg/day, i.p.) treatment for 7 consecutive days. Animals' motor activity in a novel environment was monitored after the 1st and the 7th saline/ribavirin injection. Body weight gain was calculated as appropriate. Determination and quantification of ribavirin in the brain tissue were performed too. RESULTS The 1st application of ribavirin to amphetamine-sensitized rats affected/decreased their novelty-induced motor activity only at a dose of 30 mg/kg. After the 7th application, ribavirin 30 mg/kg/day still decreased while 10 and 20 mg/kg/day increased novelty-induced motor activity. These behavioral effects coincided with the time required to reach maximum ribavirin concentration in the brain. Body weight gain during withdrawal was not influenced by any of the doses tested. CONCLUSION Ribavirin displays central effects that in repeated treatment, depending on the applied dose, could significantly influence psychomotor response but not body weight gain during psychostimulant/amphetamine withdrawal.
PB  - Bentham Science Publishers Ltd.
T2  - Current Pharmaceutical Design
T1  - A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats
IS  - 31
VL  - 26
DO  - 10.2174/1381612826666200326125821
SP  - 3884
EP  - 3894
ER  - 

@article{
author = "Petković, Branka and Kesić, Srđan and Ristić, Slavica and Pavković, Željko and Podgorac, Jelena and Stojadinović, Gordana and Pešić, Vesna",
year = "2020",
abstract = "BACKGROUND Psychotic states related to psychostimulant misuse in patients with hepatitis C virus infection may complicate acceptance and reaction to antiviral treatment. This observation equally applies to widely used ribavirin therapy. OBJECTIVE We examined psychomotor and body weight gain response to low ribavirin doses after cessation of intermittent amphetamine treatment in adult rats to assess its role in neurobehavioral outcome during psychostimulant withdrawal. METHOD The model of amphetamine-induced (1.5 mg/kg/day, i.p., 7 consecutive days) motor sensitization and affected body weight gain was established in adult male Wistar rats. Then, additional cohort of amphetamine-sensitized rats was subjected to saline (0.9% NaCl; 1 mL/kg/day; i.p.) or ribavirin (10, 20 and 30 mg/kg/day, i.p.) treatment for 7 consecutive days. Animals' motor activity in a novel environment was monitored after the 1st and the 7th saline/ribavirin injection. Body weight gain was calculated as appropriate. Determination and quantification of ribavirin in the brain tissue were performed too. RESULTS The 1st application of ribavirin to amphetamine-sensitized rats affected/decreased their novelty-induced motor activity only at a dose of 30 mg/kg. After the 7th application, ribavirin 30 mg/kg/day still decreased while 10 and 20 mg/kg/day increased novelty-induced motor activity. These behavioral effects coincided with the time required to reach maximum ribavirin concentration in the brain. Body weight gain during withdrawal was not influenced by any of the doses tested. CONCLUSION Ribavirin displays central effects that in repeated treatment, depending on the applied dose, could significantly influence psychomotor response but not body weight gain during psychostimulant/amphetamine withdrawal.",
publisher = "Bentham Science Publishers Ltd.",
journal = "Current Pharmaceutical Design",
title = "A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats",
number = "31",
volume = "26",
doi = "10.2174/1381612826666200326125821",
pages = "3884-3894"
}

Petković, B., Kesić, S., Ristić, S., Pavković, Ž., Podgorac, J., Stojadinović, G.,& Pešić, V.. (2020). A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats. in Current Pharmaceutical Design
Bentham Science Publishers Ltd.., 26(31), 3884-3894.
https://doi.org/10.2174/1381612826666200326125821

Petković B, Kesić S, Ristić S, Pavković Ž, Podgorac J, Stojadinović G, Pešić V. A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats. in Current Pharmaceutical Design. 2020;26(31):3884-3894.
doi:10.2174/1381612826666200326125821 .

Petković, Branka, Kesić, Srđan, Ristić, Slavica, Pavković, Željko, Podgorac, Jelena, Stojadinović, Gordana, Pešić, Vesna, "A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats" in Current Pharmaceutical Design, 26, no. 31 (2020):3884-3894,
https://doi.org/10.2174/1381612826666200326125821 . .

TY  - JOUR
AU  - Todorović, Smilja
AU  - Lončarević-Vasiljković, Nataša
AU  - Jović, Milena
AU  - Sokanović, Srđan
AU  - Kanazir, Selma
AU  - Mladenović, Aleksandra
PY  - 2020
UR  - https://www.sciencedirect.com/science/article/pii/S0047637419302003?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3565
AB  - Alzheimer's disease patients (AD), as well as AD transgenic mice, are characterized by increased frailty. Furthermore, the assessment of frailty status represents a feasible approach for detecting individuals prone to develop more severe form of AD and for measuring the outcome of existing and putative AD therapeutics. The 5xFAD mouse is one of the widely used transgenic animal models of AD, but frailty in this model is scantly investigated. We used two validated mouse frailty assessment tools: phenotypic frailty score (FS) and clinical frailty index (FI) to investigate age- and sex- related differences in frailty status in 5xFAD mice. These tools measure different age-related deficits and do not necessarily identify the same subpopulations as frail. We detected a significant increase in frailty with age in both sexes, although females were surprisingly less frail than males. Depending on the tools used, a notable difference in frailty status was detected, with frailty index and frailty score identifying different mice as frail. These results warrant great caution when choosing the frailty tool and point to the need for further adaptation of frailty measurements in mouse models of AD.
PB  - Elsevier
T2  - Mechanisms of Ageing and Development
T1  - Frailty index and phenotype frailty score: Sex- and age-related differences in 5XFAD transgenic mouse model of Alzheimer's disease.
VL  - 185
DO  - 10.1016/j.mad.2019.111195
SP  - 111195
ER  - 

@article{
author = "Todorović, Smilja and Lončarević-Vasiljković, Nataša and Jović, Milena and Sokanović, Srđan and Kanazir, Selma and Mladenović, Aleksandra",
year = "2020",
abstract = "Alzheimer's disease patients (AD), as well as AD transgenic mice, are characterized by increased frailty. Furthermore, the assessment of frailty status represents a feasible approach for detecting individuals prone to develop more severe form of AD and for measuring the outcome of existing and putative AD therapeutics. The 5xFAD mouse is one of the widely used transgenic animal models of AD, but frailty in this model is scantly investigated. We used two validated mouse frailty assessment tools: phenotypic frailty score (FS) and clinical frailty index (FI) to investigate age- and sex- related differences in frailty status in 5xFAD mice. These tools measure different age-related deficits and do not necessarily identify the same subpopulations as frail. We detected a significant increase in frailty with age in both sexes, although females were surprisingly less frail than males. Depending on the tools used, a notable difference in frailty status was detected, with frailty index and frailty score identifying different mice as frail. These results warrant great caution when choosing the frailty tool and point to the need for further adaptation of frailty measurements in mouse models of AD.",
publisher = "Elsevier",
journal = "Mechanisms of Ageing and Development",
title = "Frailty index and phenotype frailty score: Sex- and age-related differences in 5XFAD transgenic mouse model of Alzheimer's disease.",
volume = "185",
doi = "10.1016/j.mad.2019.111195",
pages = "111195"
}

Todorović, S., Lončarević-Vasiljković, N., Jović, M., Sokanović, S., Kanazir, S.,& Mladenović, A.. (2020). Frailty index and phenotype frailty score: Sex- and age-related differences in 5XFAD transgenic mouse model of Alzheimer's disease.. in Mechanisms of Ageing and Development
Elsevier., 185, 111195.
https://doi.org/10.1016/j.mad.2019.111195

Todorović S, Lončarević-Vasiljković N, Jović M, Sokanović S, Kanazir S, Mladenović A. Frailty index and phenotype frailty score: Sex- and age-related differences in 5XFAD transgenic mouse model of Alzheimer's disease.. in Mechanisms of Ageing and Development. 2020;185:111195.
doi:10.1016/j.mad.2019.111195 .

Todorović, Smilja, Lončarević-Vasiljković, Nataša, Jović, Milena, Sokanović, Srđan, Kanazir, Selma, Mladenović, Aleksandra, "Frailty index and phenotype frailty score: Sex- and age-related differences in 5XFAD transgenic mouse model of Alzheimer's disease." in Mechanisms of Ageing and Development, 185 (2020):111195,
https://doi.org/10.1016/j.mad.2019.111195 . .

TY  - JOUR
AU  - Perović, Milka
AU  - Jović, Milena
AU  - Todorović, Smilja
AU  - Mladenović, Aleksandra
AU  - Milanović, Desanka
AU  - Kanazir, Selma
AU  - Lončarević-Vasiljković, Nataša
PY  - 2020
UR  - https://www.tandfonline.com/doi/abs/10.1080/1028415X.2020.1769410
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32476608
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3760
AB  - OBJECTIVE Traumatic brain injury (TBI) is one of the most common causes of neurological damage in young and middle aged people. Food restriction (FR) has been shown to act neuroprotectively in animal models of stroke and TBI. Indeed, our previous studies showed that FR attenuates inflammation, through suppression of microglial activation and TNF-α production, suppresses caspase-3-induced neuronal cell death and enhances neuroplasticity in the rat model of TBI. Glucocorticoids (GCs) play a central role in mediating both molecular and behavioral responses to food restriction. However, the exact mechanisms of FR neuroprotection in TBI are still unclear. The goal of the present study was to examine whether FR exerts its beneficial effects by altering the glucocorticoid receptor (GR) signaling alone and/or together with other protective factors. METHODS To this end, we examined the effects of FR (50% of regular daily food intake for 3 months prior to TBI) on the protein levels of total GR, GR phosphoisoform Ser232 (p-GR) and its transcriptional activity, as well as 11β-HSD1, NFκB (p65) and HSP70 as factors related to the GR signaling. RESULTS Our results demonstrate that FR applied prior to TBI significantly changes p-GR levels, and it's transcriptional activity during the recovery period after TBI. Moreover, as a pretreatment, FR modulates other protective factors in response to TBI, such as 11β-HSD1, NF-κB (p65) and HSP70 that act in parallel with GR in it's anti-inflammatory and neuroprotective effects in the rat model of brain injury. CONCLUSION Our results suggest that prophylactic FR represents a potent non-invasive approach capable of changing GR signalling, together with other factors related to the GR signaling in the model of TBI.
PB  - Taylor and Francis Ltd.
T2  - Nutritional Neuroscience
T1  - Neuroprotective effects of food restriction in a rat model of traumatic brain injury - the role of glucocorticoid signaling.
DO  - 10.1080/1028415X.2020.1769410
ER  - 

@article{
author = "Perović, Milka and Jović, Milena and Todorović, Smilja and Mladenović, Aleksandra and Milanović, Desanka and Kanazir, Selma and Lončarević-Vasiljković, Nataša",
year = "2020",
abstract = "OBJECTIVE Traumatic brain injury (TBI) is one of the most common causes of neurological damage in young and middle aged people. Food restriction (FR) has been shown to act neuroprotectively in animal models of stroke and TBI. Indeed, our previous studies showed that FR attenuates inflammation, through suppression of microglial activation and TNF-α production, suppresses caspase-3-induced neuronal cell death and enhances neuroplasticity in the rat model of TBI. Glucocorticoids (GCs) play a central role in mediating both molecular and behavioral responses to food restriction. However, the exact mechanisms of FR neuroprotection in TBI are still unclear. The goal of the present study was to examine whether FR exerts its beneficial effects by altering the glucocorticoid receptor (GR) signaling alone and/or together with other protective factors. METHODS To this end, we examined the effects of FR (50% of regular daily food intake for 3 months prior to TBI) on the protein levels of total GR, GR phosphoisoform Ser232 (p-GR) and its transcriptional activity, as well as 11β-HSD1, NFκB (p65) and HSP70 as factors related to the GR signaling. RESULTS Our results demonstrate that FR applied prior to TBI significantly changes p-GR levels, and it's transcriptional activity during the recovery period after TBI. Moreover, as a pretreatment, FR modulates other protective factors in response to TBI, such as 11β-HSD1, NF-κB (p65) and HSP70 that act in parallel with GR in it's anti-inflammatory and neuroprotective effects in the rat model of brain injury. CONCLUSION Our results suggest that prophylactic FR represents a potent non-invasive approach capable of changing GR signalling, together with other factors related to the GR signaling in the model of TBI.",
publisher = "Taylor and Francis Ltd.",
journal = "Nutritional Neuroscience",
title = "Neuroprotective effects of food restriction in a rat model of traumatic brain injury - the role of glucocorticoid signaling.",
doi = "10.1080/1028415X.2020.1769410"
}

Perović, M., Jović, M., Todorović, S., Mladenović, A., Milanović, D., Kanazir, S.,& Lončarević-Vasiljković, N.. (2020). Neuroprotective effects of food restriction in a rat model of traumatic brain injury - the role of glucocorticoid signaling.. in Nutritional Neuroscience
Taylor and Francis Ltd...
https://doi.org/10.1080/1028415X.2020.1769410

Perović M, Jović M, Todorović S, Mladenović A, Milanović D, Kanazir S, Lončarević-Vasiljković N. Neuroprotective effects of food restriction in a rat model of traumatic brain injury - the role of glucocorticoid signaling.. in Nutritional Neuroscience. 2020;.
doi:10.1080/1028415X.2020.1769410 .

Perović, Milka, Jović, Milena, Todorović, Smilja, Mladenović, Aleksandra, Milanović, Desanka, Kanazir, Selma, Lončarević-Vasiljković, Nataša, "Neuroprotective effects of food restriction in a rat model of traumatic brain injury - the role of glucocorticoid signaling." in Nutritional Neuroscience (2020),
https://doi.org/10.1080/1028415X.2020.1769410 . .

TY  - JOUR
AU  - Petković, Branka
AU  - Kesić, Srđan
AU  - Ristić, Slavica
AU  - Pavković, Željko
AU  - Podgorac, Jelena
AU  - Stojadinović, Gordana
AU  - Pešić, Vesna
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3765
AB  - Background: Psychotic states related to psychostimulant misuse in patients with hepatitis C virus infection may complicate acceptance and reaction to antiviral treatment. This observation equally applies to widely used ribavirin therapy.
Objective: We examined psychomotor and body weight gain response to low ribavirin doses after cessation of intermittent amphetamine treatment in adult rats to assess its role in neurobehavioral outcome during psychostimulant withdrawal.
Method: The model of amphetamine-induced (1.5 mg/kg/day, i.p., 7 consecutive days) motor sensitization and affected body weight gain was established in adult male Wistar rats. Then, additional cohort of amphetamine-sensitized rats was subjected to saline (0.9% NaCl; 1 mL/kg/day; i.p.) or ribavirin (10, 20 and 30 mg/kg/day, i.p.) treatment for 7 consecutive days. Animals’ motor activity in a novel environment was monitored after the 1st and the 7th saline/ribavirin injection. Body weight gain was calculated as appropriate. Determination and quantification of ribavirin in the brain tissue were performed too.
Results: The 1st application of ribavirin to amphetamine-sensitized rats affected/decreased their novelty-induced motor activity only at a dose of 30 mg/kg. After the 7th application, ribavirin 30 mg/kg/day still decreased while 10 and 20 mg/kg/day increased novelty-induced motor activity. These behavioral effects coincided with the time required to reach maximum ribavirin concentration in the brain. Body weight gain during withdrawal was not influenced by any of the doses tested.
Conclusion: Ribavirin displays central effects that in repeated treatment, depending on the applied dose, could significantly influence psychomotor response but not body weight gain during psychostimulant/amphetamine withdrawal.
PB  - Bentham Science Publishers Ltd.
T2  - Current Pharmaceutical Design
T1  - A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats
DO  - 10.2174/1381612826666200326125821
ER  - 

@article{
author = "Petković, Branka and Kesić, Srđan and Ristić, Slavica and Pavković, Željko and Podgorac, Jelena and Stojadinović, Gordana and Pešić, Vesna",
year = "2020",
abstract = "Background: Psychotic states related to psychostimulant misuse in patients with hepatitis C virus infection may complicate acceptance and reaction to antiviral treatment. This observation equally applies to widely used ribavirin therapy.
Objective: We examined psychomotor and body weight gain response to low ribavirin doses after cessation of intermittent amphetamine treatment in adult rats to assess its role in neurobehavioral outcome during psychostimulant withdrawal.
Method: The model of amphetamine-induced (1.5 mg/kg/day, i.p., 7 consecutive days) motor sensitization and affected body weight gain was established in adult male Wistar rats. Then, additional cohort of amphetamine-sensitized rats was subjected to saline (0.9% NaCl; 1 mL/kg/day; i.p.) or ribavirin (10, 20 and 30 mg/kg/day, i.p.) treatment for 7 consecutive days. Animals’ motor activity in a novel environment was monitored after the 1st and the 7th saline/ribavirin injection. Body weight gain was calculated as appropriate. Determination and quantification of ribavirin in the brain tissue were performed too.
Results: The 1st application of ribavirin to amphetamine-sensitized rats affected/decreased their novelty-induced motor activity only at a dose of 30 mg/kg. After the 7th application, ribavirin 30 mg/kg/day still decreased while 10 and 20 mg/kg/day increased novelty-induced motor activity. These behavioral effects coincided with the time required to reach maximum ribavirin concentration in the brain. Body weight gain during withdrawal was not influenced by any of the doses tested.
Conclusion: Ribavirin displays central effects that in repeated treatment, depending on the applied dose, could significantly influence psychomotor response but not body weight gain during psychostimulant/amphetamine withdrawal.",
publisher = "Bentham Science Publishers Ltd.",
journal = "Current Pharmaceutical Design",
title = "A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats",
doi = "10.2174/1381612826666200326125821"
}

Petković, B., Kesić, S., Ristić, S., Pavković, Ž., Podgorac, J., Stojadinović, G.,& Pešić, V.. (2020). A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats. in Current Pharmaceutical Design
Bentham Science Publishers Ltd...
https://doi.org/10.2174/1381612826666200326125821

Petković B, Kesić S, Ristić S, Pavković Ž, Podgorac J, Stojadinović G, Pešić V. A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats. in Current Pharmaceutical Design. 2020;.
doi:10.2174/1381612826666200326125821 .

Petković, Branka, Kesić, Srđan, Ristić, Slavica, Pavković, Željko, Podgorac, Jelena, Stojadinović, Gordana, Pešić, Vesna, "A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats" in Current Pharmaceutical Design (2020),
https://doi.org/10.2174/1381612826666200326125821 . .

TY  - JOUR
AU  - Petković, Branka
AU  - Kesić, Srđan
AU  - Pešić, Vesna
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3642
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3665
AB  - Substance-use disorder represents a frequently hidden non-communicable chronic disease. Patients with intravenous drug addiction are at high risk of direct exposure to a variety of viral infections and are considered to be the largest subpopulation infected with the hepatitis C virus. Ribavirin is a synthetic nucleoside analog that has been used as an integral component of hepatitis C therapy. However, ribavirin medication is quite often associated with pronounced psychiatric adverse effects. It is not well understood to what extent ribavirin per se contributes to changes in drug-related neurobehavioral disturbances, especially in the case of psychostimulant drugs such as amphetamine. It is now well-known that repeated amphetamine usage produces psychosis in humans and behavioral sensitization in animals. On the other hand, ribavirin has an affinity for adenosine A1 receptors that antagonistically modulate the activity of dopamine D1 receptors, which play a critical role in the development of behavioral sensitization. This review will focus on the current knowledge of neurochemical/neurobiological changes that exist in the psychostimulant drug-addicted brain itself and the antipsychotic-like efficiency of adenosine agonists. Particular attention will be paid to the potential side effects of ribavirin therapy, and the opportunities and challenges related to its application in already existing psychostimulant-use disorder.
PB  - Bentham Science Publishers Ltd.
T2  - Current Pharmaceutical Design
T1  - Critical View on the Usage of Ribavirin in Already Existing Psychostimulant-Use Disorder
IS  - 4
VL  - 26
DO  - 10.2174/1381612826666200115094642
SP  - 466
EP  - 484
ER  - 

@article{
author = "Petković, Branka and Kesić, Srđan and Pešić, Vesna",
year = "2020",
abstract = "Substance-use disorder represents a frequently hidden non-communicable chronic disease. Patients with intravenous drug addiction are at high risk of direct exposure to a variety of viral infections and are considered to be the largest subpopulation infected with the hepatitis C virus. Ribavirin is a synthetic nucleoside analog that has been used as an integral component of hepatitis C therapy. However, ribavirin medication is quite often associated with pronounced psychiatric adverse effects. It is not well understood to what extent ribavirin per se contributes to changes in drug-related neurobehavioral disturbances, especially in the case of psychostimulant drugs such as amphetamine. It is now well-known that repeated amphetamine usage produces psychosis in humans and behavioral sensitization in animals. On the other hand, ribavirin has an affinity for adenosine A1 receptors that antagonistically modulate the activity of dopamine D1 receptors, which play a critical role in the development of behavioral sensitization. This review will focus on the current knowledge of neurochemical/neurobiological changes that exist in the psychostimulant drug-addicted brain itself and the antipsychotic-like efficiency of adenosine agonists. Particular attention will be paid to the potential side effects of ribavirin therapy, and the opportunities and challenges related to its application in already existing psychostimulant-use disorder.",
publisher = "Bentham Science Publishers Ltd.",
journal = "Current Pharmaceutical Design",
title = "Critical View on the Usage of Ribavirin in Already Existing Psychostimulant-Use Disorder",
number = "4",
volume = "26",
doi = "10.2174/1381612826666200115094642",
pages = "466-484"
}

Petković, B., Kesić, S.,& Pešić, V.. (2020). Critical View on the Usage of Ribavirin in Already Existing Psychostimulant-Use Disorder. in Current Pharmaceutical Design
Bentham Science Publishers Ltd.., 26(4), 466-484.
https://doi.org/10.2174/1381612826666200115094642

Petković B, Kesić S, Pešić V. Critical View on the Usage of Ribavirin in Already Existing Psychostimulant-Use Disorder. in Current Pharmaceutical Design. 2020;26(4):466-484.
doi:10.2174/1381612826666200115094642 .

Petković, Branka, Kesić, Srđan, Pešić, Vesna, "Critical View on the Usage of Ribavirin in Already Existing Psychostimulant-Use Disorder" in Current Pharmaceutical Design, 26, no. 4 (2020):466-484,
https://doi.org/10.2174/1381612826666200115094642 . .

TY  - JOUR
AU  - Lazić, Divna
AU  - Tešić, Vesna
AU  - Jovanović, Mirna
AU  - Brkić, Marjana
AU  - Milanović, Desanka
AU  - Zloković, Berislav V.
AU  - Kanazir, Selma
AU  - Perović, Milka
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/31931140
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3596
AB  - Food restriction has been widely associated with beneficial effects on brain aging and age-related neurodegenerative diseases such as Alzheimer's disease. However, previous studies on the effects of food restriction on aging- or pathology-related cognitive decline are controversial, emphasizing the importance of the type, onset and duration of food restriction. In the present study, we assessed the effects of preventive every-other-day (EOD) feeding regimen on neurodegenerative phenotype in 5XFAD transgenic mice, a commonly used mouse model of Alzheimer's disease. EOD feeding regimen was introduced to transgenic female mice at the age of 2 months and the effects on amyloid-β (Aβ) accumulation, gliosis, synaptic plasticity, and blood-brain barrier breakdown were analyzed in cortical tissue of 6-month-old animals. Surprisingly, significant increase of inflammation in the cortex of 5XFAD fed EOD mice was observed, reflected by the expression of microglial and astrocytic markers. This increase in reactivity and/or proliferation of glial cells was accompanied by an increase in proinflammatory cytokine TNF-α, p38 MAPK and EAAT2, and a decrease in GAD67. NMDA receptor subunit 2B, related to glutamate excitotoxicity, was increased in the cortex of 5XFAD-EOD mice indicating additional alterations in glutamatergic signaling. Furthermore, 4 months of EOD feeding regimen had led to synaptic plasticity proteins reduction and neuronal injury in 5XFAD mice. However, EOD feeding regimen did not affect Aβ load and blood-brain barrier permeability in the cortex of 5XFAD mice. Our results demonstrate that EOD feeding regimen exacerbates Alzheimer's disease-like neurodegenerative and neuroinflammatory changes irrespective of Aβ pathology in 5XFAD mice, suggesting that caution should be paid when using food restrictions in the prodromal phase of this neurodegenerative disease.
T2  - Neurobiology of Disease
T1  - Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease.
VL  - 136
DO  - 10.1016/j.nbd.2020.104745
SP  - 104745
ER  - 

@article{
author = "Lazić, Divna and Tešić, Vesna and Jovanović, Mirna and Brkić, Marjana and Milanović, Desanka and Zloković, Berislav V. and Kanazir, Selma and Perović, Milka",
year = "2020",
abstract = "Food restriction has been widely associated with beneficial effects on brain aging and age-related neurodegenerative diseases such as Alzheimer's disease. However, previous studies on the effects of food restriction on aging- or pathology-related cognitive decline are controversial, emphasizing the importance of the type, onset and duration of food restriction. In the present study, we assessed the effects of preventive every-other-day (EOD) feeding regimen on neurodegenerative phenotype in 5XFAD transgenic mice, a commonly used mouse model of Alzheimer's disease. EOD feeding regimen was introduced to transgenic female mice at the age of 2 months and the effects on amyloid-β (Aβ) accumulation, gliosis, synaptic plasticity, and blood-brain barrier breakdown were analyzed in cortical tissue of 6-month-old animals. Surprisingly, significant increase of inflammation in the cortex of 5XFAD fed EOD mice was observed, reflected by the expression of microglial and astrocytic markers. This increase in reactivity and/or proliferation of glial cells was accompanied by an increase in proinflammatory cytokine TNF-α, p38 MAPK and EAAT2, and a decrease in GAD67. NMDA receptor subunit 2B, related to glutamate excitotoxicity, was increased in the cortex of 5XFAD-EOD mice indicating additional alterations in glutamatergic signaling. Furthermore, 4 months of EOD feeding regimen had led to synaptic plasticity proteins reduction and neuronal injury in 5XFAD mice. However, EOD feeding regimen did not affect Aβ load and blood-brain barrier permeability in the cortex of 5XFAD mice. Our results demonstrate that EOD feeding regimen exacerbates Alzheimer's disease-like neurodegenerative and neuroinflammatory changes irrespective of Aβ pathology in 5XFAD mice, suggesting that caution should be paid when using food restrictions in the prodromal phase of this neurodegenerative disease.",
journal = "Neurobiology of Disease",
title = "Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease.",
volume = "136",
doi = "10.1016/j.nbd.2020.104745",
pages = "104745"
}

Lazić, D., Tešić, V., Jovanović, M., Brkić, M., Milanović, D., Zloković, B. V., Kanazir, S.,& Perović, M.. (2020). Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease.. in Neurobiology of Disease, 136, 104745.
https://doi.org/10.1016/j.nbd.2020.104745

Lazić D, Tešić V, Jovanović M, Brkić M, Milanović D, Zloković BV, Kanazir S, Perović M. Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease.. in Neurobiology of Disease. 2020;136:104745.
doi:10.1016/j.nbd.2020.104745 .

Lazić, Divna, Tešić, Vesna, Jovanović, Mirna, Brkić, Marjana, Milanović, Desanka, Zloković, Berislav V., Kanazir, Selma, Perović, Milka, "Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease." in Neurobiology of Disease, 136 (2020):104745,
https://doi.org/10.1016/j.nbd.2020.104745 . .

TY  - JOUR
AU  - Rakić, Mia
AU  - Monje, Alberto
AU  - Radovanović, Sandro
AU  - Petković-Ćurčin, Aleksandra
AU  - Vojvodić, Danilo
AU  - Tatić, Zoran
PY  - 2020
UR  - https://pubmed.ncbi.nlm.nih.gov/31773730/
UR  - http://www.ncbi.nlm.nih.gov/pubmed/31773730
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3828
AB  - BACKGROUND Study objectives were 1) to estimate diagnostic capacity of clinical parameters, receptor activator of nuclear factor kappa-B (RANKL) and osteoprotegerin (OPG) to diagnose healthy peri-implant condition (HI), peri-implant mucositis (PIM) and peri-implantitis (PIMP) by assessing respective diagnostic accuracy, sensitivity, specificity and diagnostic ranges 2) to develop personalized diagnostic model (PDM) for implant monitoring. METHODS Split-mouth study included 126 patients and 252 implants (HI = 126, PIM = 57, and PIMP = 69). RANKL and OPG concentrations were estimated in peri-implant crevicular fluid using enzyme-linked immunosorbent assay method and assessed with clinical parameters using routine statistics, while the diagnostic capacity of individual parameters and overall clinical diagnosis were estimated using classifying algorithms. PDM was developed using decision trees. RESULTS Bleeding on probing (BOP), plaque index, and probing depth (PD) were confirmed reliable discriminants between peri-implant health and disease, while increase in PD (PD > 4 mm) and suppuration were good discriminants amongst PIM/PIMP. Bone turnover markers (BTMs) demonstrated presence of bone resorption in PIM; between comparable diagnostic ranges PIM/PIMP, PIMP was clinically distinguished from PIM in about 60% of patients while 40% remained diagnosed as false negatives. PDM demonstrated highest diagnostic capacity (accuracy: 96.27%, sensitivity: 95.00%, specificity: 100%) and defined HI: BOP ≤0.25%; PIM: BOP >0.25%, PD ≤4.5 mm; PIMP: BOP >0.25%, PD >4.5 mm and RANKL ≤19.9 pg/site; PIM: BOP >0.25%, PD >4.5 mm, and RANKL >19.9 pg/site. CONCLUSIONS BTMs demonstrated capacity to substantially improve clinical diagnosis of peri-implant conditions. Considering lack of difference in BTMs between PIM/PIMP and cluster of PIM with exceeding BTMs, a more refined definition of peri-implant conditions according to biological characteristics is required for further BTMs validation and appropriate PIMP management.
PB  - Wiley-Blackwell
T2  - Journal of Periodontology
T1  - Is the personalized approach the key to improve clinical diagnosis of peri-implant conditions? The role of bone markers.
IS  - 7
VL  - 91
DO  - 10.1002/JPER.19-0283
SP  - 859
EP  - 869
ER  - 

@article{
author = "Rakić, Mia and Monje, Alberto and Radovanović, Sandro and Petković-Ćurčin, Aleksandra and Vojvodić, Danilo and Tatić, Zoran",
year = "2020",
abstract = "BACKGROUND Study objectives were 1) to estimate diagnostic capacity of clinical parameters, receptor activator of nuclear factor kappa-B (RANKL) and osteoprotegerin (OPG) to diagnose healthy peri-implant condition (HI), peri-implant mucositis (PIM) and peri-implantitis (PIMP) by assessing respective diagnostic accuracy, sensitivity, specificity and diagnostic ranges 2) to develop personalized diagnostic model (PDM) for implant monitoring. METHODS Split-mouth study included 126 patients and 252 implants (HI = 126, PIM = 57, and PIMP = 69). RANKL and OPG concentrations were estimated in peri-implant crevicular fluid using enzyme-linked immunosorbent assay method and assessed with clinical parameters using routine statistics, while the diagnostic capacity of individual parameters and overall clinical diagnosis were estimated using classifying algorithms. PDM was developed using decision trees. RESULTS Bleeding on probing (BOP), plaque index, and probing depth (PD) were confirmed reliable discriminants between peri-implant health and disease, while increase in PD (PD > 4 mm) and suppuration were good discriminants amongst PIM/PIMP. Bone turnover markers (BTMs) demonstrated presence of bone resorption in PIM; between comparable diagnostic ranges PIM/PIMP, PIMP was clinically distinguished from PIM in about 60% of patients while 40% remained diagnosed as false negatives. PDM demonstrated highest diagnostic capacity (accuracy: 96.27%, sensitivity: 95.00%, specificity: 100%) and defined HI: BOP ≤0.25%; PIM: BOP >0.25%, PD ≤4.5 mm; PIMP: BOP >0.25%, PD >4.5 mm and RANKL ≤19.9 pg/site; PIM: BOP >0.25%, PD >4.5 mm, and RANKL >19.9 pg/site. CONCLUSIONS BTMs demonstrated capacity to substantially improve clinical diagnosis of peri-implant conditions. Considering lack of difference in BTMs between PIM/PIMP and cluster of PIM with exceeding BTMs, a more refined definition of peri-implant conditions according to biological characteristics is required for further BTMs validation and appropriate PIMP management.",
publisher = "Wiley-Blackwell",
journal = "Journal of Periodontology",
title = "Is the personalized approach the key to improve clinical diagnosis of peri-implant conditions? The role of bone markers.",
number = "7",
volume = "91",
doi = "10.1002/JPER.19-0283",
pages = "859-869"
}

Rakić, M., Monje, A., Radovanović, S., Petković-Ćurčin, A., Vojvodić, D.,& Tatić, Z.. (2020). Is the personalized approach the key to improve clinical diagnosis of peri-implant conditions? The role of bone markers.. in Journal of Periodontology
Wiley-Blackwell., 91(7), 859-869.
https://doi.org/10.1002/JPER.19-0283

Rakić M, Monje A, Radovanović S, Petković-Ćurčin A, Vojvodić D, Tatić Z. Is the personalized approach the key to improve clinical diagnosis of peri-implant conditions? The role of bone markers.. in Journal of Periodontology. 2020;91(7):859-869.
doi:10.1002/JPER.19-0283 .

Rakić, Mia, Monje, Alberto, Radovanović, Sandro, Petković-Ćurčin, Aleksandra, Vojvodić, Danilo, Tatić, Zoran, "Is the personalized approach the key to improve clinical diagnosis of peri-implant conditions? The role of bone markers." in Journal of Periodontology, 91, no. 7 (2020):859-869,
https://doi.org/10.1002/JPER.19-0283 . .

TY  - CONF
AU  - Srbovan, Maja
AU  - Prpa, Ksenija
AU  - Tešić, Vesna
AU  - Milanović, Desanka
AU  - Perović, Milka
AU  - Kanazir, Selma
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5908
AB  - Aim: Food restriction has been widely associated with beneficial effects on brain aging and age-related neurodegenerative diseases such as Alzheimer’s disease (AD). In the present study, the effects of every-other-day (EOD) feeding regimen were studied in the hippocampus of 5XFAD mice, a well characterized animal model of AD. Parvalbumin (PV) inhibitory interneurons that are crucial for maintaining proper excitatory/inhibitory balance were examined.
Methods: Female 5xFAD mice (Tg) and their non-transgenic littermates (non-Tg) were exposed to ad libitum (AL) or intermittent, EOD feeding regimen, beginning at 2 months of age. Neurons expressing PV were detected by immunohistochemistry, in the dorsal hippocampus of 6-month-old animals. The number of parvalbumin-expressing neurons was determined independently in CA1, CA3, and DG hippocampal subregions.
Results: Immunohistochemical analysis revealed a substantial increase in the number of parvalbumin inhibitory neurons in the dorsal hippocampus of Tg-AL mice in comparison to non-Tg animals. In Tg-EOD mice, however, alterations in the number of PV-expressing neurons were subregion-specific comparing to Tg-AL mice of the same age.
Conlusions: The results of our study clearly indicate that PV-expressing interneurons are of importance in further understanding of neural basis of AD-like-associated cognitive impairments and EOD-induced effects in 5xFAD mouse model of AD.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - The effect of intermittent feeding on the number of parvalbumin-expressing neurons in the hippocampus of 5XFAD mice
IS  - 299
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5908
ER  - 

@conference{
author = "Srbovan, Maja and Prpa, Ksenija and Tešić, Vesna and Milanović, Desanka and Perović, Milka and Kanazir, Selma",
year = "2019",
abstract = "Aim: Food restriction has been widely associated with beneficial effects on brain aging and age-related neurodegenerative diseases such as Alzheimer’s disease (AD). In the present study, the effects of every-other-day (EOD) feeding regimen were studied in the hippocampus of 5XFAD mice, a well characterized animal model of AD. Parvalbumin (PV) inhibitory interneurons that are crucial for maintaining proper excitatory/inhibitory balance were examined.
Methods: Female 5xFAD mice (Tg) and their non-transgenic littermates (non-Tg) were exposed to ad libitum (AL) or intermittent, EOD feeding regimen, beginning at 2 months of age. Neurons expressing PV were detected by immunohistochemistry, in the dorsal hippocampus of 6-month-old animals. The number of parvalbumin-expressing neurons was determined independently in CA1, CA3, and DG hippocampal subregions.
Results: Immunohistochemical analysis revealed a substantial increase in the number of parvalbumin inhibitory neurons in the dorsal hippocampus of Tg-AL mice in comparison to non-Tg animals. In Tg-EOD mice, however, alterations in the number of PV-expressing neurons were subregion-specific comparing to Tg-AL mice of the same age.
Conlusions: The results of our study clearly indicate that PV-expressing interneurons are of importance in further understanding of neural basis of AD-like-associated cognitive impairments and EOD-induced effects in 5xFAD mouse model of AD.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "The effect of intermittent feeding on the number of parvalbumin-expressing neurons in the hippocampus of 5XFAD mice",
number = "299",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5908"
}

Srbovan, M., Prpa, K., Tešić, V., Milanović, D., Perović, M.,& Kanazir, S.. (2019). The effect of intermittent feeding on the number of parvalbumin-expressing neurons in the hippocampus of 5XFAD mice. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society.(299).
https://hdl.handle.net/21.15107/rcub_ibiss_5908

Srbovan M, Prpa K, Tešić V, Milanović D, Perović M, Kanazir S. The effect of intermittent feeding on the number of parvalbumin-expressing neurons in the hippocampus of 5XFAD mice. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;(299).
https://hdl.handle.net/21.15107/rcub_ibiss_5908 .

Srbovan, Maja, Prpa, Ksenija, Tešić, Vesna, Milanović, Desanka, Perović, Milka, Kanazir, Selma, "The effect of intermittent feeding on the number of parvalbumin-expressing neurons in the hippocampus of 5XFAD mice" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia, no. 299 (2019),
https://hdl.handle.net/21.15107/rcub_ibiss_5908 .

TY  - CONF
AU  - Jović, Milena
AU  - Lončarević-Vasiljković, Nataša
AU  - Ivković, Sanja
AU  - Milanović, Desanka
AU  - Kanazir, Selma
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5803
AB  - Aims: Alzheimer’s disease (AD) is the most prevalent type of dementia in elderly,triggered by multiple factors such as amyloid 
plaques, neurofibrillary tangles and neuroinflammation. The use of supplements with omega-3 fatty acids has been associated 
with reduced risk and lessened AD pathology. The purpose of this study was to elucidate the mechanisms underlying effects of 
short-term fish oil (FO) suplementation in presymptomatic stage of AD in 5xFAD mice.
Methods: Three-month old female 5xFAD mice received FO (100μl/animal/day) via oral gavage during the period of 3 weeks. 
Western blot and immunohistochemical analysis were used to detect changes in pathological features of AD in cortex of 5xFAD 
mice. AmiloGlo was used to visualize plaques. Amyloid beta (Aβ) peptide, dystrophic neurites (DNs), microglia/macrophages 
and CX3CR1/CX3CL1 were detect by anti-Aβ42-, anti-SMI31-, p-Tau-, anti-Iba-1-, anti-CX3CR1 anti-CX3CL1 antibodies, 
retrospectively. Immunostaining was observed by confocal microscopy. Quantification was done by Image J and Image Quant 
softwer. 
Results: The present study shows that short-term FO supplementation applied in presymptomatic stage of AD, alters the 
behaviour of microglia/macrophages prompting them to establish a physical barrier around amyloid plaques. This barrier 
significantly suppresses DNs formation through the reduction of both Aβ content and tau hyperphosphorylation. Moreover, the 
short-term FO treatment suppresses CX3CR1/CX3CL1 axis, interaction between microglial cells and neurons, which represents 
one of possible mechanisms for altered microglial/macrophage motility and colocalization around plaques.
Conclusion: Our findings suggest that FO consumption may play an important role in modulating microglial response and 
ameliorating the AD pathology in presymptomatic stage of Alzheimer’s disease.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Mechanism underlying effects of fish oil supplementation in presymptomatic stage of Alzheimer disease in 5XFAD mice
SP  - 287
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5803
ER  - 

@conference{
author = "Jović, Milena and Lončarević-Vasiljković, Nataša and Ivković, Sanja and Milanović, Desanka and Kanazir, Selma",
year = "2019",
abstract = "Aims: Alzheimer’s disease (AD) is the most prevalent type of dementia in elderly,triggered by multiple factors such as amyloid 
plaques, neurofibrillary tangles and neuroinflammation. The use of supplements with omega-3 fatty acids has been associated 
with reduced risk and lessened AD pathology. The purpose of this study was to elucidate the mechanisms underlying effects of 
short-term fish oil (FO) suplementation in presymptomatic stage of AD in 5xFAD mice.
Methods: Three-month old female 5xFAD mice received FO (100μl/animal/day) via oral gavage during the period of 3 weeks. 
Western blot and immunohistochemical analysis were used to detect changes in pathological features of AD in cortex of 5xFAD 
mice. AmiloGlo was used to visualize plaques. Amyloid beta (Aβ) peptide, dystrophic neurites (DNs), microglia/macrophages 
and CX3CR1/CX3CL1 were detect by anti-Aβ42-, anti-SMI31-, p-Tau-, anti-Iba-1-, anti-CX3CR1 anti-CX3CL1 antibodies, 
retrospectively. Immunostaining was observed by confocal microscopy. Quantification was done by Image J and Image Quant 
softwer. 
Results: The present study shows that short-term FO supplementation applied in presymptomatic stage of AD, alters the 
behaviour of microglia/macrophages prompting them to establish a physical barrier around amyloid plaques. This barrier 
significantly suppresses DNs formation through the reduction of both Aβ content and tau hyperphosphorylation. Moreover, the 
short-term FO treatment suppresses CX3CR1/CX3CL1 axis, interaction between microglial cells and neurons, which represents 
one of possible mechanisms for altered microglial/macrophage motility and colocalization around plaques.
Conclusion: Our findings suggest that FO consumption may play an important role in modulating microglial response and 
ameliorating the AD pathology in presymptomatic stage of Alzheimer’s disease.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Mechanism underlying effects of fish oil supplementation in presymptomatic stage of Alzheimer disease in 5XFAD mice",
pages = "287",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5803"
}

Jović, M., Lončarević-Vasiljković, N., Ivković, S., Milanović, D.,& Kanazir, S.. (2019). Mechanism underlying effects of fish oil supplementation in presymptomatic stage of Alzheimer disease in 5XFAD mice. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 287.
https://hdl.handle.net/21.15107/rcub_ibiss_5803

Jović M, Lončarević-Vasiljković N, Ivković S, Milanović D, Kanazir S. Mechanism underlying effects of fish oil supplementation in presymptomatic stage of Alzheimer disease in 5XFAD mice. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:287.
https://hdl.handle.net/21.15107/rcub_ibiss_5803 .

Jović, Milena, Lončarević-Vasiljković, Nataša, Ivković, Sanja, Milanović, Desanka, Kanazir, Selma, "Mechanism underlying effects of fish oil supplementation in presymptomatic stage of Alzheimer disease in 5XFAD mice" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):287,
https://hdl.handle.net/21.15107/rcub_ibiss_5803 .

TY  - CONF
AU  - Prvulović, Milica
AU  - Smiljanić, Kosara
AU  - Todorović, Smilja
AU  - Kanazir, Selma
AU  - Mladenović, Aleksandra
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5717
AB  - Aims: Dietary restriction (DR) has numerous beneficial effects on organism, starting from positive effect on life expectancy, to protective effects on cardiovascular system, blood lipid levels, immune response, glucoregulation, and neurological functions. Previously it has been shown that DR changes expression of genes and proteins involved in cholesterol metabolism, in both cerebral cortex and hippocampus. Herein we investigated cholesterol homeostasis in  cerebellum, as a brain structure involved in motor and cognitive functions. 
Methods: We examined the effect of 4 different DR regimens (intermittent fasting and limited daily feeding of various onset and duration), on cholesterol metabolism in cerebellum of aging male Wistar rats. We used western blot to examine changes in the level of proteins playing the major roles in cholesterol biosynthesis (SREBP1 and HMGCR), transport (ApoE and LRP1) and elimination from the brain (CYP46).
Results: Detected changes in the expression level of selected proteins indicated that the effect of DR is highly dependent on the type of dietary regimen and the age when implemented. Positive effect is mainly noticed in the group of 18 months old rats.
Conclusions: This study showed the potential of dietary restriction as an alternative to pharmacological treatment of high blood cholesterol levels  and confirmed beneficial effects of DR as a  healthy lifestyle in prevention of age related disorders.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - The effects of different dietary regimens on cholesterol metabolism in the cerebellum of aging rats
SP  - 497
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5717
ER  - 

@conference{
author = "Prvulović, Milica and Smiljanić, Kosara and Todorović, Smilja and Kanazir, Selma and Mladenović, Aleksandra",
year = "2019",
abstract = "Aims: Dietary restriction (DR) has numerous beneficial effects on organism, starting from positive effect on life expectancy, to protective effects on cardiovascular system, blood lipid levels, immune response, glucoregulation, and neurological functions. Previously it has been shown that DR changes expression of genes and proteins involved in cholesterol metabolism, in both cerebral cortex and hippocampus. Herein we investigated cholesterol homeostasis in  cerebellum, as a brain structure involved in motor and cognitive functions. 
Methods: We examined the effect of 4 different DR regimens (intermittent fasting and limited daily feeding of various onset and duration), on cholesterol metabolism in cerebellum of aging male Wistar rats. We used western blot to examine changes in the level of proteins playing the major roles in cholesterol biosynthesis (SREBP1 and HMGCR), transport (ApoE and LRP1) and elimination from the brain (CYP46).
Results: Detected changes in the expression level of selected proteins indicated that the effect of DR is highly dependent on the type of dietary regimen and the age when implemented. Positive effect is mainly noticed in the group of 18 months old rats.
Conclusions: This study showed the potential of dietary restriction as an alternative to pharmacological treatment of high blood cholesterol levels  and confirmed beneficial effects of DR as a  healthy lifestyle in prevention of age related disorders.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "The effects of different dietary regimens on cholesterol metabolism in the cerebellum of aging rats",
pages = "497",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5717"
}

Prvulović, M., Smiljanić, K., Todorović, S., Kanazir, S.,& Mladenović, A.. (2019). The effects of different dietary regimens on cholesterol metabolism in the cerebellum of aging rats. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society., 497.
https://hdl.handle.net/21.15107/rcub_ibiss_5717

Prvulović M, Smiljanić K, Todorović S, Kanazir S, Mladenović A. The effects of different dietary regimens on cholesterol metabolism in the cerebellum of aging rats. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:497.
https://hdl.handle.net/21.15107/rcub_ibiss_5717 .

Prvulović, Milica, Smiljanić, Kosara, Todorović, Smilja, Kanazir, Selma, Mladenović, Aleksandra, "The effects of different dietary regimens on cholesterol metabolism in the cerebellum of aging rats" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):497,
https://hdl.handle.net/21.15107/rcub_ibiss_5717 .

TY  - THES
AU  - Todorović, Smilja
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3375
AB  - Starenje je normalan, fiziološki proces koji obuhvata sve organe i organske sisteme i tokom koga se organizam suočava sa nizom strukturnih i funkcionalnih promena. Starenje mozga je izrazito kompleksan proces, predstavljen nizom sukcesivnih događaja koji postepeno rezultiraju gubitkom kognitivnih i motornih funkcija. Postoji niz farmakoloških i sredinskih faktora koji su u stanju da odlože i/ili uspore mnoge od starosno-zavisnih procesa, a dijetalna restrikcija (DR) je jedna od najviše i najduže istraživanih. Mnogobrojni su eksperimentalni i epidemiološki podaci koji govore u prilog korisnih efekata restriktivnog režima ishrane, bez obzira da li se radi o svakodnevnoj, ili intermitentnoj dijeti, smanjenju količine hrane ili kalorija. Međutim, u poslednje vreme se sve više pojavljuju podaci koji dovode u pitanje univerzalnost korisnog dejstva dijete. Da bi ovakva intervencija postigla svoj optimalni efekat, neophodno je povesti računa o određenim specifičnostima prilikom uspostavljanja restriktivnog režima ishrane. Pre svega, pokazano je da stepen restrikcije igra bitnu ulogu u efektima koje ona proizvodi i da previše restriktivan režim ishrane može imati negativne posledice po organizam. Takođe, postoje indicije da nisu svi organski sistemi podjednako podložni procesima starenja, kao ni dejstvu dijete. Efekat dijete se može veoma razlikovati u zavisnosti od stepena i tipa restrikcije, pola i organa gde se efekat očekuje, kao i od starosti jedinke na koju se restriktivni režim primenjuje. Prvi korak u istraživanju korisnih efekata restrikcije hrane koja je iznosila 60% prosečnog dnevnog unosa hrane, bio je ispitati efekat različitih dijetalnih režima, odnosno efekte DR koja je različito trajala i koja je započeta u različitim životnim dobima kod mužjaka Wistar soja pacova. Praćen je čitav niz parametara u aktivnosti životinja i detektovane su značajne razlike u njihovim fizičkim i kognitivnim preformansama, kako tokom starenja, tako i pod uticajem različitih režima ishrane. Dugotrajna dijetalna restrikcija otpočeta u adultnom dobu je dovela do poboljšanja u izvođenju motoričkih i kognitivnih testova i do sveukupnog poboljšanog stanja organizma, što se ogledalo u smanjenoj krhkosti ovih životinja. Nasuprot tome, restriktivni režimi istog tipa, ali kasnijeg početka i/ili kraćeg trajanja, pokazali su se kao neuspešni u pokušaju da se izazovu korisni efekti i poboljša stanje organizma. Dijeta sa izrazito kasnim početkom i kratkog trajanja je dovela čak i do negativnih posledica po organizam, izazivajući dodatne poteškoće u habituaciji životinja i povečavajući njihovu krhkost. Shodno detektovanim rezultatima, za dalji nastavak istraživanja je izabrana dijeta za koju je pokazano da daje nedvosmisleno dobar efekat i dalje je ispitivan njen uticaj na energetski metabolizam mozga. Smatra se da je narušavanje homeostaze energetskog metabolizma jedan od vodećih uzroka koji leži u osnovi brojnih neurodegenerativnih bolesti koje se javljaju tokom starenja. Ključnu ulogu u metabolizmu glukoze i održavanju energetske homeostaze imaju proteini insulinskog signalnog puta koji su odgovorni za regulaciju unosa hranjivih materija, zatim AMPK kao glavni energetski senzor ćelije i glukozni transporteri koji omogućavaju ulazak glukoze u mozak i nervne ćelije. Novija istraživanja ukazuju da pomenuti proteini imaju važnu ulogu u procesima koji leže u osnovi efekata DR na starosno-zavisne promene. Upravo zato, važan aspekt ove doktorske disertacije predstavljao je ispitivanje promena u ekspresiji glukoznih transportera, AMPK proteina, Neuropeptida Y, insulina, insulinskog receptora, supstrata insulinskog receptora i protein kinaze B. Ispitivanja su sprovedena na nivou kore prednjeg mozga, hipokampusa i hipotalamusa, struktura u kojima je pokazano da dolazi do znatnog narušavanja energetske homeostaze tokom starenja. Dobijene promene su sagledane u odnosu na promene relevantnih biohemijskih parametara u serumu, kao što su glukoza, insulin, holesterol i trigliceridi. Zaključeno je da dugotrajna dijetalna restrikcija dovodi do niza promena, koje uključuju povećanje nivoa NPY proteina i insulina, utišavanje insulinskog signalnog puta u hipotalamusu i hipokampusu, kao i do bolje snabdevenost kore velikog mozga i hipokampusa dovoljnom količinom energije. Sve ove promene su zajedno doprinele poboljšanju kognitivnih i motoričkih performansi životinja u dubokoj starosti. Rezultati ove doktorske disertacije upućuju na korisnost restriktivnog režima ishrane, ali istovremeno nameću limite u pogledu trenutka uvođenja ovakvog režima ishrane i dužine trajanja, uzimajući u obzir negativne efekte do kojih DR može dovesti u određenim slučajevima.
AB  - Aging is a normal, physiological process that involves all organs and organic systems, and during which the organism faces a number of structural and functional changes. Brain aging is an extremely complex process, represented by a series of successive events that gradually result in loss of cognitive and motor functions. There are a number of pharmacological and environmental factors that are able to postpone and / or slow down many of the age-dependent processes, and dietary restriction (DR) is one of the most investigated and most widely used experimental intervention in aging research. There are numerous experimental and epidemiological data that support the beneficial effects of a restrictive diet, regardless of the type: a daily reduction or intermittent diet, reduction in food or in calories, all of those approaches seem beneficial. Nevertheless, there is a body of data that challenges current premise about comprehensive DR usefulness. In order for DR to achieve its optimal effect, it is necessary to take certain specificities into account while establishing a restrictive dietary regime. First of all, it has been shown that the percentage of restriction plays an important role in the effects it induces, and that a very restrictive diet may have negative consequences for the organism. In addition, not all the body systems are equally susceptible to aging processes, nor to the beneficial effects of DR. The effect of the restrictive diet can vary greatly, depending on the degree and type of restriction, gender and organs examined, as well as the age of the individual to which the restrictive regimen is applied. In order to investigate the effect of 60% DR on the energy homeostasis and insulin signaling in the brain, we first examined the effects of three different types of dietary restriction that varied in length and onset, on rat behavior during aging. The experiments were performed on 12-, 18- and 24-month-old male Wistar rats exposed to AL or DR type of feeding (60% of AL daily intake). A variety of parameters were monitored in the activities of animals and significant differences in their physical and cognitive performance were detected, both during aging and under the influence of different dietary regimes. Long-term dietary restriction that started in young adulthood led to the improvement of motor and cognitive performances and to the reduced frailty. By contrast, restrictive regimes of the same type, but with late-onset and/or the shorter duration, have a less pronounced positive impact on motor and cognitive functions during aging. A diet that started at old age and had the shortest duration has even led to negative consequences, causing additional difficulties in the habituation of animals, and increased their frailty score. Based on results mentioned above and the most favorable outcome of DR, we continued to investigate the longest dietary regime and its effect on brain metabolism during aging. Disruption of homeostasis in the brain energy metabolism is considered to be one of the leading causes that lie behind many age-related neurodegenerative diseases. The key proteins that regulate processes of glucose metabolism and energy homeostasis are: AMPK, as the main energy cell sensor, glucose transporters that facilitate glucose transport across the blood-brain-barrier and plasma membrane, and proteins involved in insulin signaling pathway, responsible for the regulation of nutrient intake. These proteins play an important role in processes involved in the effects of DR on age-dependent changes. For this reason, we examined changes in the expression of glucose transporters, AMPK protein, Neuropeptide Y, insulin, Insulin Receptor, Insulin Receptor Substrate, and Protein Kinase B. The analysis was performed in cerebral cortex, hippocampus and hypothalamus, structures most severely affected by process of aging and also with important role in energy homeostasis. Relevant biochemical parameters in the serum were also investigated, such as glucose, insulin, cholesterol, and triglycerides. The most pronounced changes elicited by long-term restrictive regime were related to increased levels of insulin and NPY proteins, as well as attenuation of the insulin signal pathway in the hypothalamus and the hippocampus, and improved energy supply of cortex and hippocampus. All the above changes resulted in a significant improvement of cognitive and motor performances of 24 month-old animals. The results of this doctoral dissertation point to the usefulness of a restrictive diet, but at the same time impose certain limits, regarding the time point when the diet should be applied and also the duration of diet, taking into account the negative effects that DR may have in certain cases.
PB  - Belgrade: University of Belgrade, Faculty of Biology
T2  - University of Belgrade, Faculty of Biology
T1  - Uticaj dugotrajne dijetalne restrikcije na insulinski signalni put u mozgu pacova tokom starenja
T1  - The effect of long-term dietary restriction on insulin signaling pathway in rat brain during aging
SP  - 1
EP  - 155
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3375
ER  - 

@phdthesis{
author = "Todorović, Smilja",
year = "2019",
abstract = "Starenje je normalan, fiziološki proces koji obuhvata sve organe i organske sisteme i tokom koga se organizam suočava sa nizom strukturnih i funkcionalnih promena. Starenje mozga je izrazito kompleksan proces, predstavljen nizom sukcesivnih događaja koji postepeno rezultiraju gubitkom kognitivnih i motornih funkcija. Postoji niz farmakoloških i sredinskih faktora koji su u stanju da odlože i/ili uspore mnoge od starosno-zavisnih procesa, a dijetalna restrikcija (DR) je jedna od najviše i najduže istraživanih. Mnogobrojni su eksperimentalni i epidemiološki podaci koji govore u prilog korisnih efekata restriktivnog režima ishrane, bez obzira da li se radi o svakodnevnoj, ili intermitentnoj dijeti, smanjenju količine hrane ili kalorija. Međutim, u poslednje vreme se sve više pojavljuju podaci koji dovode u pitanje univerzalnost korisnog dejstva dijete. Da bi ovakva intervencija postigla svoj optimalni efekat, neophodno je povesti računa o određenim specifičnostima prilikom uspostavljanja restriktivnog režima ishrane. Pre svega, pokazano je da stepen restrikcije igra bitnu ulogu u efektima koje ona proizvodi i da previše restriktivan režim ishrane može imati negativne posledice po organizam. Takođe, postoje indicije da nisu svi organski sistemi podjednako podložni procesima starenja, kao ni dejstvu dijete. Efekat dijete se može veoma razlikovati u zavisnosti od stepena i tipa restrikcije, pola i organa gde se efekat očekuje, kao i od starosti jedinke na koju se restriktivni režim primenjuje. Prvi korak u istraživanju korisnih efekata restrikcije hrane koja je iznosila 60% prosečnog dnevnog unosa hrane, bio je ispitati efekat različitih dijetalnih režima, odnosno efekte DR koja je različito trajala i koja je započeta u različitim životnim dobima kod mužjaka Wistar soja pacova. Praćen je čitav niz parametara u aktivnosti životinja i detektovane su značajne razlike u njihovim fizičkim i kognitivnim preformansama, kako tokom starenja, tako i pod uticajem različitih režima ishrane. Dugotrajna dijetalna restrikcija otpočeta u adultnom dobu je dovela do poboljšanja u izvođenju motoričkih i kognitivnih testova i do sveukupnog poboljšanog stanja organizma, što se ogledalo u smanjenoj krhkosti ovih životinja. Nasuprot tome, restriktivni režimi istog tipa, ali kasnijeg početka i/ili kraćeg trajanja, pokazali su se kao neuspešni u pokušaju da se izazovu korisni efekti i poboljša stanje organizma. Dijeta sa izrazito kasnim početkom i kratkog trajanja je dovela čak i do negativnih posledica po organizam, izazivajući dodatne poteškoće u habituaciji životinja i povečavajući njihovu krhkost. Shodno detektovanim rezultatima, za dalji nastavak istraživanja je izabrana dijeta za koju je pokazano da daje nedvosmisleno dobar efekat i dalje je ispitivan njen uticaj na energetski metabolizam mozga. Smatra se da je narušavanje homeostaze energetskog metabolizma jedan od vodećih uzroka koji leži u osnovi brojnih neurodegenerativnih bolesti koje se javljaju tokom starenja. Ključnu ulogu u metabolizmu glukoze i održavanju energetske homeostaze imaju proteini insulinskog signalnog puta koji su odgovorni za regulaciju unosa hranjivih materija, zatim AMPK kao glavni energetski senzor ćelije i glukozni transporteri koji omogućavaju ulazak glukoze u mozak i nervne ćelije. Novija istraživanja ukazuju da pomenuti proteini imaju važnu ulogu u procesima koji leže u osnovi efekata DR na starosno-zavisne promene. Upravo zato, važan aspekt ove doktorske disertacije predstavljao je ispitivanje promena u ekspresiji glukoznih transportera, AMPK proteina, Neuropeptida Y, insulina, insulinskog receptora, supstrata insulinskog receptora i protein kinaze B. Ispitivanja su sprovedena na nivou kore prednjeg mozga, hipokampusa i hipotalamusa, struktura u kojima je pokazano da dolazi do znatnog narušavanja energetske homeostaze tokom starenja. Dobijene promene su sagledane u odnosu na promene relevantnih biohemijskih parametara u serumu, kao što su glukoza, insulin, holesterol i trigliceridi. Zaključeno je da dugotrajna dijetalna restrikcija dovodi do niza promena, koje uključuju povećanje nivoa NPY proteina i insulina, utišavanje insulinskog signalnog puta u hipotalamusu i hipokampusu, kao i do bolje snabdevenost kore velikog mozga i hipokampusa dovoljnom količinom energije. Sve ove promene su zajedno doprinele poboljšanju kognitivnih i motoričkih performansi životinja u dubokoj starosti. Rezultati ove doktorske disertacije upućuju na korisnost restriktivnog režima ishrane, ali istovremeno nameću limite u pogledu trenutka uvođenja ovakvog režima ishrane i dužine trajanja, uzimajući u obzir negativne efekte do kojih DR može dovesti u određenim slučajevima., Aging is a normal, physiological process that involves all organs and organic systems, and during which the organism faces a number of structural and functional changes. Brain aging is an extremely complex process, represented by a series of successive events that gradually result in loss of cognitive and motor functions. There are a number of pharmacological and environmental factors that are able to postpone and / or slow down many of the age-dependent processes, and dietary restriction (DR) is one of the most investigated and most widely used experimental intervention in aging research. There are numerous experimental and epidemiological data that support the beneficial effects of a restrictive diet, regardless of the type: a daily reduction or intermittent diet, reduction in food or in calories, all of those approaches seem beneficial. Nevertheless, there is a body of data that challenges current premise about comprehensive DR usefulness. In order for DR to achieve its optimal effect, it is necessary to take certain specificities into account while establishing a restrictive dietary regime. First of all, it has been shown that the percentage of restriction plays an important role in the effects it induces, and that a very restrictive diet may have negative consequences for the organism. In addition, not all the body systems are equally susceptible to aging processes, nor to the beneficial effects of DR. The effect of the restrictive diet can vary greatly, depending on the degree and type of restriction, gender and organs examined, as well as the age of the individual to which the restrictive regimen is applied. In order to investigate the effect of 60% DR on the energy homeostasis and insulin signaling in the brain, we first examined the effects of three different types of dietary restriction that varied in length and onset, on rat behavior during aging. The experiments were performed on 12-, 18- and 24-month-old male Wistar rats exposed to AL or DR type of feeding (60% of AL daily intake). A variety of parameters were monitored in the activities of animals and significant differences in their physical and cognitive performance were detected, both during aging and under the influence of different dietary regimes. Long-term dietary restriction that started in young adulthood led to the improvement of motor and cognitive performances and to the reduced frailty. By contrast, restrictive regimes of the same type, but with late-onset and/or the shorter duration, have a less pronounced positive impact on motor and cognitive functions during aging. A diet that started at old age and had the shortest duration has even led to negative consequences, causing additional difficulties in the habituation of animals, and increased their frailty score. Based on results mentioned above and the most favorable outcome of DR, we continued to investigate the longest dietary regime and its effect on brain metabolism during aging. Disruption of homeostasis in the brain energy metabolism is considered to be one of the leading causes that lie behind many age-related neurodegenerative diseases. The key proteins that regulate processes of glucose metabolism and energy homeostasis are: AMPK, as the main energy cell sensor, glucose transporters that facilitate glucose transport across the blood-brain-barrier and plasma membrane, and proteins involved in insulin signaling pathway, responsible for the regulation of nutrient intake. These proteins play an important role in processes involved in the effects of DR on age-dependent changes. For this reason, we examined changes in the expression of glucose transporters, AMPK protein, Neuropeptide Y, insulin, Insulin Receptor, Insulin Receptor Substrate, and Protein Kinase B. The analysis was performed in cerebral cortex, hippocampus and hypothalamus, structures most severely affected by process of aging and also with important role in energy homeostasis. Relevant biochemical parameters in the serum were also investigated, such as glucose, insulin, cholesterol, and triglycerides. The most pronounced changes elicited by long-term restrictive regime were related to increased levels of insulin and NPY proteins, as well as attenuation of the insulin signal pathway in the hypothalamus and the hippocampus, and improved energy supply of cortex and hippocampus. All the above changes resulted in a significant improvement of cognitive and motor performances of 24 month-old animals. The results of this doctoral dissertation point to the usefulness of a restrictive diet, but at the same time impose certain limits, regarding the time point when the diet should be applied and also the duration of diet, taking into account the negative effects that DR may have in certain cases.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "Uticaj dugotrajne dijetalne restrikcije na insulinski signalni put u mozgu pacova tokom starenja, The effect of long-term dietary restriction on insulin signaling pathway in rat brain during aging",
pages = "1-155",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3375"
}

Todorović, S.. (2019). Uticaj dugotrajne dijetalne restrikcije na insulinski signalni put u mozgu pacova tokom starenja. in University of Belgrade, Faculty of Biology
Belgrade: University of Belgrade, Faculty of Biology., 1-155.
https://hdl.handle.net/21.15107/rcub_ibiss_3375

Todorović S. Uticaj dugotrajne dijetalne restrikcije na insulinski signalni put u mozgu pacova tokom starenja. in University of Belgrade, Faculty of Biology. 2019;:1-155.
https://hdl.handle.net/21.15107/rcub_ibiss_3375 .

Todorović, Smilja, "Uticaj dugotrajne dijetalne restrikcije na insulinski signalni put u mozgu pacova tokom starenja" in University of Belgrade, Faculty of Biology (2019):1-155,
https://hdl.handle.net/21.15107/rcub_ibiss_3375 .

TY  - THES
AU  - Lazić, Divna
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3527
AB  - Krvno-moždana barijera (KMB) je ključna strukturna i funkcionalna prilagođenost krvnih sudova u centralnom nervnom sistemu, neophodna za njegovo normalno funkcionisanje. Osnovni zadatak KMB je da spreči slobodan prolazak humoralnih i hemijskih faktora i ćelija iz krvi u moždani parenhim i obrnuto. Periciti su ćelije koje naležu na endotelne ćelije krvnih kapilara, i zajedno sa endotelnim ćelijama, kao i proširenjima astrocitnih nastavaka i bazalnom membranom, čine KMB. Periciti, osim uloge u svim aspektima funkcionisanja i propustljivosti KMB, imaju ulogu u regulaciji protoka krvi, angiogeneze, čišćenja toksičnih materija iz mozga, neuroinflamaciji, kontrolišu ekspresiju proteina poreklom iz endotelnih ćelija koji ulaze u sastav adherentnih i čvrstih veza endotelnog sloja, a opisana su i njihova svojstva slična nervnim matičnim ćelijama. Alchajmerova bolest (AB) je neurodegenerativno oboljenje i najčešći oblik demencije kod ljudi starijih od 65 godina. AB se na neuropatološkom nalazu karakteriše akumulacijom vanćelijskog amiloida β i unutarćelijskog tau proteina u moždanom tkivu, kao i gubitkom neurona. Dodatno, istraživanja su pokazala da se promene u moždanoj cirkulaciji, protoku krvi i propustljivosti kapilara mogu primetiti i pre pojave kliničke slike sporadičnog oblika AB. Cilj ove teze je bio da se ispita integritet KMB i uloga percita u prisustvu i odsustvu AB patologije. Dodatni cilj je bio i da se ispita uloga PICALM proteina, jer se pokazalo da mutacije u ne-kodirajućem regionu PICALM gena mogu da predstavljaju faktor rizika za razvoj AB u kasnijem dobu (eng. late-onset). Uloga PICALM-a je praćena zasebno na endotelnim ćelijama i neuronima, a ispitana je i posledica farmakološkog povećanja ekspresije PICALM-a na nivo amiloida β. Konačno, ispitana je dijetalna restrikcija kao potencijalna intervencija u cilju smanjenja patologije vezane za AB. Da bi se ispitala uloga pericita korišćena su dva mišija modela: a) životinje koje imaju mutacije u receptoru PDGFRβ, koji je specifično eksprimiran na pericitima i vaskularnim glatkim mišićnim ćelijama i ima ključnu ulogu u regulaciji ćelijskog ciklusa, diferencijacije, rasta i razvoja i b) novouspostavljeni model akutnog gubitka pericita. Dodatno, da bi se ispitali poremećaji KMB u AB, korišćene su transgene životinje kao modeli AB - Tg2576, 3xTg i 5XFAD koje imaju jednu ili više mutacija u genima amiloidnog prekursorkog proteina i presenilina. Da bi se ispitale uloge PICALM-a u endotelnim ćelijama i neuronima, korišćeni su specijalni transgeni sojevi koji eksprimiraju Cre rekombinazu pod promotorom koji se specifično nalazi u endotelnim ćelijama (Cdh5-Cre) i neuronima (Camk2a-CreER), kako bi se osigurala specifična delecija PICALM-a iz ovih ćelija. Dijetalni režim ishrane svaki drugi dan (eng. every-other-day, EOD), je bio primenjen na ženke 5XFAD miševa. Svi eksperimenti su uključivali i odgovarajuće kontrolne životinje iz istog okota, a rezultati su prikupljeni analizom imunoblotova, imunohistohemijkih i histoloških bojenja, i testova ponašanja. Rezultati su pokazali da hronični gubitak pericita dovodi do demijelinizacije neuronskih nastavaka u beloj masi mozga, što dovodi do poremećaja u ponašanju, a da akutni gubitak pericita u adultnom životu može da dovede do gubitka nervnih ćelija u korteksu i hipokampusu i poremećaja u memoriji koja zavisi od normalne funkcije hipokampusa. Ispitivanje propustljivosti KMBumodelima AB je pokazalo, pored „klasične“ patologije – akumulacije amiloida, i izraženu narušenost KMB, čak i pre gubitka neurona. Dalje su rezultati otkrili da je PICALM protein izuzetno važan za čišćenje amiloida iz moždanog parenhima i da farmakološko povećanje ekspresije PICALM-a dovodi do smanjene količine amiloida u mozgu. Takođe, prisustvo PICALM-a u neuronima je važno za normalno ponašanje i zdravlje neurona. Primena dijetalne intervencije nije pokazala pozitivne efekte na smanjenje AB patologije. Naprotiv, ovakva intervencija je izazvala veću inflamaciju i dovela do drastičnog pada sinaptičkih proteina i čak smrti neurona kod ženki 5XFAD soja. Rezultati prikazani u ovoj disertaciji ukazuju na važnost održanja ne samo strukturnog integriteta KMB, već i optimalnog nivoa proteina koji ulaze u sastav ćelija KMB. Dodatno, rezultati ukazuju da promene na KMB mogu da dovedu do funkcionalnih promena i u odsustvu patologije izazvane Ab. Takođe, s obzirom da svi ispitani modeli AB imaju promene na KMB, važno je da se uključi i ova komponenta prilikom dijagnostifikovanja AB. Na kraju, iako je dijetalna restrikcija u prethodnim rezultatima pokazala uglavnom odlaganje ili umanjenje AB patologije; pol i starost jedinke, kao i tip i dužina trajanja dijetalne restrikcije treba pažljivo da se uzme u obzir pre odluke da se uvede kao tretman.
AB  - The blood-brain barrier (BBB) is a key structural and functional adaptation of blood vessels in the central nervous system, necessary for its normal functioning. The basic task of BBB is to prevent the free passage of humoral and chemical factors and cells from the blood into the brain parenchyma and vice versa. Pericytes are cells that attach to the endothelial cells of the blood capillaries, and together with the endothelial cells, as well as astrocytic end-feet and the basement membrane, constitute BBB. Pericytes, in addition to their role in all aspects of the functioning and permeability of BBB, play a role in regulation of blood flow, angiogenesis, clearance of toxic substances from the brain, neuroinflammation, control the expression of various proteins in endothelial cells, especially adherent and tight junctions proteins of the endothelial layer, and their properties similar to nerve stem cells are also described. Alzheimer's disease (AD) is a neurodegenerative disease and the most common form of dementia in people over 65 years of age. AD on neuropathological findings is characterized by accumulation of extracellular amyloid β and intracellular tau protein in brain tissue, as well as neuronal loss. In addition, studies have shown that changes in cerebral circulation, blood flow, and capillary permeability can be observed even before the onset of clinical presentation of sporadic AD. The aim of this thesis was to investigate the integrity of BBB and the role of pericytes in the presence and absence of AD pathology. Additional aim was to investigate the role of PICALM proteins, as it has been shown that mutations in the non-coding region of the PICALM gene may represent a risk factor for the development of late-onset AD. The role of PICALM was studied separately on endothelial cells and neurons, and the consequence of the pharmacological increase in PICALM expression to amyloid β levels was examined. Finally, dietary restriction was examined as a potential intervention to reduce ADrelated pathology. Two mouse models were used to examine the role of pericyte: a) animals that have mutations in the PDGFRβ receptor, which is specifically expressed on pericytes and vascular smooth muscle cells and plays a key role in cell cycle regulation, differentiation, growth and development, and b) newly established model of acute pericyte loss. Additionally, to examine KMB disorders in AD, transgenic animals were used as models of AD - Tg2576, 3xTg, and 5XFAD that have one or more mutations in the genes of amyloid precursor protein and presenilin. To examine the roles of PICALM in endothelial cells and neurons, special transgenic strains expressing Cre recombinase were used under a promoter specifically found in endothelial cells (Cdh5-Cre) and neurons (Camk2a-CreER), to provide specific deletion of PICALM from these cells. Every-other-day (EOD) diet regimen was administered to female 5XFAD mice. All experiments included appropriate control animals from the same litter, and the results were acquired by immunoblot analysis, immunohistochemical and histological staining, and behavioral tests. The results showed that chronic loss of pericytes leads to demyelination of neural processes in the brain white matter, which leads to behavioral deficits, and that acute loss of pericytes in adult brain can lead to loss of neurons in the cortex and hippocampus, and hippocampal-dependent memory deficits. Analysis of BBB permeability in AD models revealed, that in addition to "classical" pathology - amyloid accumulation, there is a significant BBB breakdown, which often occurs even before neuronal loss. The results further revealed that the PICALM protein is extremely important for the clearance of amyloid from the brain parenchyma and that the pharmacological increase in PICALM expression leads to a decreased level of amyloid in the brain. Also, the presence of PICALM in neurons is important for the normal behavior and neuronal health. And lastly, the use of dietary intervention showed no positive effects on the reduction of AB pathology. On the contrary, such an intervention caused greater inflammation and led to a drastic fall in synaptic proteins and even neuronal death in females of the 5XFAD strain. The results presented in this dissertation indicate the importance of maintaining not only the structural integrity of BBB, but also the optimal level of proteins expressed within different cells of BBB cells. In addition, the results indicate that changes in BBB can lead to functional changes even in the absence of pathology caused by Ab. Also, since all AD models tested in this study showed BBB breakdown, it is important to include this component when diagnosing AD. Lastly, although dietary restriction in the previous results showed a major delay or reduction of AD pathology; the sex and age of the individual as well as the type and length of dietary restriction should be carefully considered before deciding to introduce it as a treatment.
PB  - Belgrade: University of Belgrade, Faculty of Biology
T2  - University of Belgrade, Faculty of Biology
T1  - Doprinos poremećaja krvno-moždane barijere patofiziologiji Alchajmerove bolesti u transgenim animalnim modelima
T1  - Contribution of blood-brain barrier disruption to the pathophysiology of Alzheimer’s disease in transgenic animal models
SP  - 1
EP  - 163
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3527
ER  - 

@phdthesis{
author = "Lazić, Divna",
year = "2019",
abstract = "Krvno-moždana barijera (KMB) je ključna strukturna i funkcionalna prilagođenost krvnih sudova u centralnom nervnom sistemu, neophodna za njegovo normalno funkcionisanje. Osnovni zadatak KMB je da spreči slobodan prolazak humoralnih i hemijskih faktora i ćelija iz krvi u moždani parenhim i obrnuto. Periciti su ćelije koje naležu na endotelne ćelije krvnih kapilara, i zajedno sa endotelnim ćelijama, kao i proširenjima astrocitnih nastavaka i bazalnom membranom, čine KMB. Periciti, osim uloge u svim aspektima funkcionisanja i propustljivosti KMB, imaju ulogu u regulaciji protoka krvi, angiogeneze, čišćenja toksičnih materija iz mozga, neuroinflamaciji, kontrolišu ekspresiju proteina poreklom iz endotelnih ćelija koji ulaze u sastav adherentnih i čvrstih veza endotelnog sloja, a opisana su i njihova svojstva slična nervnim matičnim ćelijama. Alchajmerova bolest (AB) je neurodegenerativno oboljenje i najčešći oblik demencije kod ljudi starijih od 65 godina. AB se na neuropatološkom nalazu karakteriše akumulacijom vanćelijskog amiloida β i unutarćelijskog tau proteina u moždanom tkivu, kao i gubitkom neurona. Dodatno, istraživanja su pokazala da se promene u moždanoj cirkulaciji, protoku krvi i propustljivosti kapilara mogu primetiti i pre pojave kliničke slike sporadičnog oblika AB. Cilj ove teze je bio da se ispita integritet KMB i uloga percita u prisustvu i odsustvu AB patologije. Dodatni cilj je bio i da se ispita uloga PICALM proteina, jer se pokazalo da mutacije u ne-kodirajućem regionu PICALM gena mogu da predstavljaju faktor rizika za razvoj AB u kasnijem dobu (eng. late-onset). Uloga PICALM-a je praćena zasebno na endotelnim ćelijama i neuronima, a ispitana je i posledica farmakološkog povećanja ekspresije PICALM-a na nivo amiloida β. Konačno, ispitana je dijetalna restrikcija kao potencijalna intervencija u cilju smanjenja patologije vezane za AB. Da bi se ispitala uloga pericita korišćena su dva mišija modela: a) životinje koje imaju mutacije u receptoru PDGFRβ, koji je specifično eksprimiran na pericitima i vaskularnim glatkim mišićnim ćelijama i ima ključnu ulogu u regulaciji ćelijskog ciklusa, diferencijacije, rasta i razvoja i b) novouspostavljeni model akutnog gubitka pericita. Dodatno, da bi se ispitali poremećaji KMB u AB, korišćene su transgene životinje kao modeli AB - Tg2576, 3xTg i 5XFAD koje imaju jednu ili više mutacija u genima amiloidnog prekursorkog proteina i presenilina. Da bi se ispitale uloge PICALM-a u endotelnim ćelijama i neuronima, korišćeni su specijalni transgeni sojevi koji eksprimiraju Cre rekombinazu pod promotorom koji se specifično nalazi u endotelnim ćelijama (Cdh5-Cre) i neuronima (Camk2a-CreER), kako bi se osigurala specifična delecija PICALM-a iz ovih ćelija. Dijetalni režim ishrane svaki drugi dan (eng. every-other-day, EOD), je bio primenjen na ženke 5XFAD miševa. Svi eksperimenti su uključivali i odgovarajuće kontrolne životinje iz istog okota, a rezultati su prikupljeni analizom imunoblotova, imunohistohemijkih i histoloških bojenja, i testova ponašanja. Rezultati su pokazali da hronični gubitak pericita dovodi do demijelinizacije neuronskih nastavaka u beloj masi mozga, što dovodi do poremećaja u ponašanju, a da akutni gubitak pericita u adultnom životu može da dovede do gubitka nervnih ćelija u korteksu i hipokampusu i poremećaja u memoriji koja zavisi od normalne funkcije hipokampusa. Ispitivanje propustljivosti KMBumodelima AB je pokazalo, pored „klasične“ patologije – akumulacije amiloida, i izraženu narušenost KMB, čak i pre gubitka neurona. Dalje su rezultati otkrili da je PICALM protein izuzetno važan za čišćenje amiloida iz moždanog parenhima i da farmakološko povećanje ekspresije PICALM-a dovodi do smanjene količine amiloida u mozgu. Takođe, prisustvo PICALM-a u neuronima je važno za normalno ponašanje i zdravlje neurona. Primena dijetalne intervencije nije pokazala pozitivne efekte na smanjenje AB patologije. Naprotiv, ovakva intervencija je izazvala veću inflamaciju i dovela do drastičnog pada sinaptičkih proteina i čak smrti neurona kod ženki 5XFAD soja. Rezultati prikazani u ovoj disertaciji ukazuju na važnost održanja ne samo strukturnog integriteta KMB, već i optimalnog nivoa proteina koji ulaze u sastav ćelija KMB. Dodatno, rezultati ukazuju da promene na KMB mogu da dovedu do funkcionalnih promena i u odsustvu patologije izazvane Ab. Takođe, s obzirom da svi ispitani modeli AB imaju promene na KMB, važno je da se uključi i ova komponenta prilikom dijagnostifikovanja AB. Na kraju, iako je dijetalna restrikcija u prethodnim rezultatima pokazala uglavnom odlaganje ili umanjenje AB patologije; pol i starost jedinke, kao i tip i dužina trajanja dijetalne restrikcije treba pažljivo da se uzme u obzir pre odluke da se uvede kao tretman., The blood-brain barrier (BBB) is a key structural and functional adaptation of blood vessels in the central nervous system, necessary for its normal functioning. The basic task of BBB is to prevent the free passage of humoral and chemical factors and cells from the blood into the brain parenchyma and vice versa. Pericytes are cells that attach to the endothelial cells of the blood capillaries, and together with the endothelial cells, as well as astrocytic end-feet and the basement membrane, constitute BBB. Pericytes, in addition to their role in all aspects of the functioning and permeability of BBB, play a role in regulation of blood flow, angiogenesis, clearance of toxic substances from the brain, neuroinflammation, control the expression of various proteins in endothelial cells, especially adherent and tight junctions proteins of the endothelial layer, and their properties similar to nerve stem cells are also described. Alzheimer's disease (AD) is a neurodegenerative disease and the most common form of dementia in people over 65 years of age. AD on neuropathological findings is characterized by accumulation of extracellular amyloid β and intracellular tau protein in brain tissue, as well as neuronal loss. In addition, studies have shown that changes in cerebral circulation, blood flow, and capillary permeability can be observed even before the onset of clinical presentation of sporadic AD. The aim of this thesis was to investigate the integrity of BBB and the role of pericytes in the presence and absence of AD pathology. Additional aim was to investigate the role of PICALM proteins, as it has been shown that mutations in the non-coding region of the PICALM gene may represent a risk factor for the development of late-onset AD. The role of PICALM was studied separately on endothelial cells and neurons, and the consequence of the pharmacological increase in PICALM expression to amyloid β levels was examined. Finally, dietary restriction was examined as a potential intervention to reduce ADrelated pathology. Two mouse models were used to examine the role of pericyte: a) animals that have mutations in the PDGFRβ receptor, which is specifically expressed on pericytes and vascular smooth muscle cells and plays a key role in cell cycle regulation, differentiation, growth and development, and b) newly established model of acute pericyte loss. Additionally, to examine KMB disorders in AD, transgenic animals were used as models of AD - Tg2576, 3xTg, and 5XFAD that have one or more mutations in the genes of amyloid precursor protein and presenilin. To examine the roles of PICALM in endothelial cells and neurons, special transgenic strains expressing Cre recombinase were used under a promoter specifically found in endothelial cells (Cdh5-Cre) and neurons (Camk2a-CreER), to provide specific deletion of PICALM from these cells. Every-other-day (EOD) diet regimen was administered to female 5XFAD mice. All experiments included appropriate control animals from the same litter, and the results were acquired by immunoblot analysis, immunohistochemical and histological staining, and behavioral tests. The results showed that chronic loss of pericytes leads to demyelination of neural processes in the brain white matter, which leads to behavioral deficits, and that acute loss of pericytes in adult brain can lead to loss of neurons in the cortex and hippocampus, and hippocampal-dependent memory deficits. Analysis of BBB permeability in AD models revealed, that in addition to "classical" pathology - amyloid accumulation, there is a significant BBB breakdown, which often occurs even before neuronal loss. The results further revealed that the PICALM protein is extremely important for the clearance of amyloid from the brain parenchyma and that the pharmacological increase in PICALM expression leads to a decreased level of amyloid in the brain. Also, the presence of PICALM in neurons is important for the normal behavior and neuronal health. And lastly, the use of dietary intervention showed no positive effects on the reduction of AB pathology. On the contrary, such an intervention caused greater inflammation and led to a drastic fall in synaptic proteins and even neuronal death in females of the 5XFAD strain. The results presented in this dissertation indicate the importance of maintaining not only the structural integrity of BBB, but also the optimal level of proteins expressed within different cells of BBB cells. In addition, the results indicate that changes in BBB can lead to functional changes even in the absence of pathology caused by Ab. Also, since all AD models tested in this study showed BBB breakdown, it is important to include this component when diagnosing AD. Lastly, although dietary restriction in the previous results showed a major delay or reduction of AD pathology; the sex and age of the individual as well as the type and length of dietary restriction should be carefully considered before deciding to introduce it as a treatment.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "Doprinos poremećaja krvno-moždane barijere patofiziologiji Alchajmerove bolesti u transgenim animalnim modelima, Contribution of blood-brain barrier disruption to the pathophysiology of Alzheimer’s disease in transgenic animal models",
pages = "1-163",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3527"
}

Lazić, D.. (2019). Doprinos poremećaja krvno-moždane barijere patofiziologiji Alchajmerove bolesti u transgenim animalnim modelima. in University of Belgrade, Faculty of Biology
Belgrade: University of Belgrade, Faculty of Biology., 1-163.
https://hdl.handle.net/21.15107/rcub_ibiss_3527

Lazić D. Doprinos poremećaja krvno-moždane barijere patofiziologiji Alchajmerove bolesti u transgenim animalnim modelima. in University of Belgrade, Faculty of Biology. 2019;:1-163.
https://hdl.handle.net/21.15107/rcub_ibiss_3527 .

Lazić, Divna, "Doprinos poremećaja krvno-moždane barijere patofiziologiji Alchajmerove bolesti u transgenim animalnim modelima" in University of Belgrade, Faculty of Biology (2019):1-163,
https://hdl.handle.net/21.15107/rcub_ibiss_3527 .

TY  - JOUR
AU  - Pavković, Željko
AU  - Potrebić, Milica
AU  - Kanazir, Selma
AU  - Pešić, Vesna
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0278584619304245?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3455
AB  - Adolescent neurodevelopment confer vulnerability to the actions of treatments that produce adaptations in neurocircuitry underlying motivation, impulsivity and reward. Considering wide usage of a sedative-hypnotic agent propofol in clinical practice, we examined whether propofol is a challenging treatment for peripubertal brain. Motivation/hedonic behavior (sucrose preference test), approach/avoidance behavior (elevated plus maze test) and response to dissociative drug phencyclidine (PCP) were studied in peripubertal rats (the rodent model of periadolescence) after propofol anesthesia exposure (PAE). Neurodegeneration (Fluoro-Jade staining) and the expression of proteins (Western blot) involved in excitatory synaptic transmission and activity-dependent synaptic stabilization in the medial prefrontal cortex (mPFC) and striatum (components of motivation/reward circuitry; process both appetitive and aversive events) were examined as well. In peripubertal rats PAE produced 1) transient brain-region specific changes in the expression of N-methyl-d-aspartate (NMDA) receptor subunits NR2A and NR2B, PSD-95 and N-cadherin, without neurotoxicity, 2) hyperlocomotor response to PCP, 3) no changes in preference for palatable 1% sucrose solution and a decrease in food eaten, 4) preference for 20% sucrose solution without changes in food eaten, 5) stretch-attended postures and open arms entries in the elevated plus maze test. Overall, these novel findings show that PAE leaves transient synaptic trace recognized as early form of synaptic plasticity related to passive drug exposure in the brain systems implicated in motivation/reward, increases drug-responsiveness, favors risk-taking and preference of novel/intense stimuli repairing otherwise present motivational deficiency. These findings accentuate multifaceted response to propofol in peripuberty and the importance of environmental stability for the most favorable neurobehavioral recovery.
T2  - Progress in Neuro-Psychopharmacology and Biological Psychiatry
T1  - Motivation, risk-taking and sensation seeking behavior in propofol anesthesia exposed peripubertal rats.
VL  - 96
DO  - 10.1016/j.pnpbp.2019.109733
SP  - 109733
ER  - 

@article{
author = "Pavković, Željko and Potrebić, Milica and Kanazir, Selma and Pešić, Vesna",
year = "2019",
abstract = "Adolescent neurodevelopment confer vulnerability to the actions of treatments that produce adaptations in neurocircuitry underlying motivation, impulsivity and reward. Considering wide usage of a sedative-hypnotic agent propofol in clinical practice, we examined whether propofol is a challenging treatment for peripubertal brain. Motivation/hedonic behavior (sucrose preference test), approach/avoidance behavior (elevated plus maze test) and response to dissociative drug phencyclidine (PCP) were studied in peripubertal rats (the rodent model of periadolescence) after propofol anesthesia exposure (PAE). Neurodegeneration (Fluoro-Jade staining) and the expression of proteins (Western blot) involved in excitatory synaptic transmission and activity-dependent synaptic stabilization in the medial prefrontal cortex (mPFC) and striatum (components of motivation/reward circuitry; process both appetitive and aversive events) were examined as well. In peripubertal rats PAE produced 1) transient brain-region specific changes in the expression of N-methyl-d-aspartate (NMDA) receptor subunits NR2A and NR2B, PSD-95 and N-cadherin, without neurotoxicity, 2) hyperlocomotor response to PCP, 3) no changes in preference for palatable 1% sucrose solution and a decrease in food eaten, 4) preference for 20% sucrose solution without changes in food eaten, 5) stretch-attended postures and open arms entries in the elevated plus maze test. Overall, these novel findings show that PAE leaves transient synaptic trace recognized as early form of synaptic plasticity related to passive drug exposure in the brain systems implicated in motivation/reward, increases drug-responsiveness, favors risk-taking and preference of novel/intense stimuli repairing otherwise present motivational deficiency. These findings accentuate multifaceted response to propofol in peripuberty and the importance of environmental stability for the most favorable neurobehavioral recovery.",
journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",
title = "Motivation, risk-taking and sensation seeking behavior in propofol anesthesia exposed peripubertal rats.",
volume = "96",
doi = "10.1016/j.pnpbp.2019.109733",
pages = "109733"
}

Pavković, Ž., Potrebić, M., Kanazir, S.,& Pešić, V.. (2019). Motivation, risk-taking and sensation seeking behavior in propofol anesthesia exposed peripubertal rats.. in Progress in Neuro-Psychopharmacology and Biological Psychiatry, 96, 109733.
https://doi.org/10.1016/j.pnpbp.2019.109733

Pavković Ž, Potrebić M, Kanazir S, Pešić V. Motivation, risk-taking and sensation seeking behavior in propofol anesthesia exposed peripubertal rats.. in Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2019;96:109733.
doi:10.1016/j.pnpbp.2019.109733 .

Pavković, Željko, Potrebić, Milica, Kanazir, Selma, Pešić, Vesna, "Motivation, risk-taking and sensation seeking behavior in propofol anesthesia exposed peripubertal rats." in Progress in Neuro-Psychopharmacology and Biological Psychiatry, 96 (2019):109733,
https://doi.org/10.1016/j.pnpbp.2019.109733 . .

TY  - JOUR
AU  - Petković, Branka
AU  - Stojadinović, Gordana
AU  - Kesić, Srđan
AU  - Ristić, Slavica
AU  - Martać, Ljiljana
AU  - Podgorac, Jelena
AU  - Pešić, Vesna
PY  - 2019
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46641900018P
UR  - http://www.serbiosoc.org.rs/arch/index.php/abs/article/view/3970
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3400
AB  - Clinically-related basic studies on the behavioral effects of ribavirin treatment are still lacking despite its wide use as an antiviral medication. This paper considers the effects of low ribavirin doses (10, 20 and 30 mg/kg/day) on psychomotor activity (novelty-induced exploratory behavior, d-amphetamine (AMPH, 1.5 mg/kg, intraperitoneal)-induced motor activity), and body weight gain in socially undisturbed adult male Wistar rats 24 h after the first, seventh and fourteenth once-a-day injection. Low doses of ribavirin were tested in an attempt to avoid the recognized systemic side effects related to high-dose usage. None of the singly applied ribavirin doses affected exploratory/spontaneous and AMPH-induced motor behavior (locomotion, stereotypy-like and vertical activity), however, body weight gain was significantly lower after treatment with 30 mg/kg of ribavirin. The 7- and 14-day treatments with 10 and 30 mg/kg/day of ribavirin significantly suppressed novelty-induced locomotion and body weight gain; the 14-day treatment with ribavirin at a dose of 30 mg/kg/ day decreased AMPH-induced stereotypy. These findings indicate that repeated application (up to 14 days) of low ribavirin doses results in low novelty-induced locomotion along with reduced weight gain, accentuating the existence of a U-shaped dose-response relationship with a prolonged duration of ribavirin treatment.
T2  - Archives of Biological Sciences
T1  - Psychomotor activity and body weight gain after exposure to low ribavirin doses in rats: role of treatment duration
IS  - 2
VL  - 71
DO  - 10.2298/ABS190205018P
SP  - 357
EP  - 368
ER  - 

@article{
author = "Petković, Branka and Stojadinović, Gordana and Kesić, Srđan and Ristić, Slavica and Martać, Ljiljana and Podgorac, Jelena and Pešić, Vesna",
year = "2019",
abstract = "Clinically-related basic studies on the behavioral effects of ribavirin treatment are still lacking despite its wide use as an antiviral medication. This paper considers the effects of low ribavirin doses (10, 20 and 30 mg/kg/day) on psychomotor activity (novelty-induced exploratory behavior, d-amphetamine (AMPH, 1.5 mg/kg, intraperitoneal)-induced motor activity), and body weight gain in socially undisturbed adult male Wistar rats 24 h after the first, seventh and fourteenth once-a-day injection. Low doses of ribavirin were tested in an attempt to avoid the recognized systemic side effects related to high-dose usage. None of the singly applied ribavirin doses affected exploratory/spontaneous and AMPH-induced motor behavior (locomotion, stereotypy-like and vertical activity), however, body weight gain was significantly lower after treatment with 30 mg/kg of ribavirin. The 7- and 14-day treatments with 10 and 30 mg/kg/day of ribavirin significantly suppressed novelty-induced locomotion and body weight gain; the 14-day treatment with ribavirin at a dose of 30 mg/kg/ day decreased AMPH-induced stereotypy. These findings indicate that repeated application (up to 14 days) of low ribavirin doses results in low novelty-induced locomotion along with reduced weight gain, accentuating the existence of a U-shaped dose-response relationship with a prolonged duration of ribavirin treatment.",
journal = "Archives of Biological Sciences",
title = "Psychomotor activity and body weight gain after exposure to low ribavirin doses in rats: role of treatment duration",
number = "2",
volume = "71",
doi = "10.2298/ABS190205018P",
pages = "357-368"
}

Petković, B., Stojadinović, G., Kesić, S., Ristić, S., Martać, L., Podgorac, J.,& Pešić, V.. (2019). Psychomotor activity and body weight gain after exposure to low ribavirin doses in rats: role of treatment duration. in Archives of Biological Sciences, 71(2), 357-368.
https://doi.org/10.2298/ABS190205018P

Petković B, Stojadinović G, Kesić S, Ristić S, Martać L, Podgorac J, Pešić V. Psychomotor activity and body weight gain after exposure to low ribavirin doses in rats: role of treatment duration. in Archives of Biological Sciences. 2019;71(2):357-368.
doi:10.2298/ABS190205018P .

Petković, Branka, Stojadinović, Gordana, Kesić, Srđan, Ristić, Slavica, Martać, Ljiljana, Podgorac, Jelena, Pešić, Vesna, "Psychomotor activity and body weight gain after exposure to low ribavirin doses in rats: role of treatment duration" in Archives of Biological Sciences, 71, no. 2 (2019):357-368,
https://doi.org/10.2298/ABS190205018P . .

TY  - JOUR
AU  - Taso, Ervin
AU  - Stefanović, Vladimir
AU  - Gaudin, Alexis
AU  - Grujić, Jovan
AU  - Maldonado, Estela
AU  - Petković-Curcin, Aleksandra
AU  - Vojvodić, Danilo
AU  - Sculean, Anton
AU  - Rakić, Mia
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0003996919309392?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3550
AB  - OBJECTIVE This controlled split-mouth study aimed to estimate the effect of caries and related treatment on concentrations of interleukin (IL)-2, interferon (IFN)-γ, IL-12, IL-17A, IL-13, IL-10, IL-6, IL-5, IL-4, IL-22, tumor necrosis factor (TNF)-α, and IL1-β in gingival crevicular fluid (GCF) of caries affected teeth before (B), 7 (7D) and 30 (30D) days post-treatment and to compare them with concentrations from healthy teeth. DESIGN Study population included 81 systemically and periodontally healthy non-smokers exhibiting at least one shallow occlusal/ inter-proximal caries and one healthy tooth from the same morphologic group at the contralateral position. Following clinical exam, the GCF samples were collected baseline as well as 7D and 30D, while the biomarker measurement was performed using multiplex flowcytometry. RESULTS Caries affected teeth exhibited significantly higher levels of IFN-γ, IL-1β, IL-2, IL-4 and IL-6 when compared to healthy teeth. Post-treatment cytokines levels showed general trend of increase when compared to baseline, that was significant for IL-22 and IL-17 at 7D, while IFN-γ was significantly increased at 7D compared to the healthy teeth. At 30D, IFN-γ, TNF-α, IL-17 and IL-4 levels were significantly increased when compared to healthy teeth, while IL-2 levels were significantly higher than baseline levels. CONCLUSION Considering significantly increased periodontal levels of inflammatory markers in caries affected teeth and in response to performed treatment, it seems that dental caries and related restorative treatment might contribute to periodontal inflammation via additive effects already in early-stage caries.
PB  - Pergamon
T2  - Archives of Oral Biology
T1  - Effect of dental caries on periodontal inflammatory status: A split-mouth study.
VL  - 110
DO  - 10.1016/j.archoralbio.2019.104620
SP  - 104620
ER  - 

@article{
author = "Taso, Ervin and Stefanović, Vladimir and Gaudin, Alexis and Grujić, Jovan and Maldonado, Estela and Petković-Curcin, Aleksandra and Vojvodić, Danilo and Sculean, Anton and Rakić, Mia",
year = "2019",
abstract = "OBJECTIVE This controlled split-mouth study aimed to estimate the effect of caries and related treatment on concentrations of interleukin (IL)-2, interferon (IFN)-γ, IL-12, IL-17A, IL-13, IL-10, IL-6, IL-5, IL-4, IL-22, tumor necrosis factor (TNF)-α, and IL1-β in gingival crevicular fluid (GCF) of caries affected teeth before (B), 7 (7D) and 30 (30D) days post-treatment and to compare them with concentrations from healthy teeth. DESIGN Study population included 81 systemically and periodontally healthy non-smokers exhibiting at least one shallow occlusal/ inter-proximal caries and one healthy tooth from the same morphologic group at the contralateral position. Following clinical exam, the GCF samples were collected baseline as well as 7D and 30D, while the biomarker measurement was performed using multiplex flowcytometry. RESULTS Caries affected teeth exhibited significantly higher levels of IFN-γ, IL-1β, IL-2, IL-4 and IL-6 when compared to healthy teeth. Post-treatment cytokines levels showed general trend of increase when compared to baseline, that was significant for IL-22 and IL-17 at 7D, while IFN-γ was significantly increased at 7D compared to the healthy teeth. At 30D, IFN-γ, TNF-α, IL-17 and IL-4 levels were significantly increased when compared to healthy teeth, while IL-2 levels were significantly higher than baseline levels. CONCLUSION Considering significantly increased periodontal levels of inflammatory markers in caries affected teeth and in response to performed treatment, it seems that dental caries and related restorative treatment might contribute to periodontal inflammation via additive effects already in early-stage caries.",
publisher = "Pergamon",
journal = "Archives of Oral Biology",
title = "Effect of dental caries on periodontal inflammatory status: A split-mouth study.",
volume = "110",
doi = "10.1016/j.archoralbio.2019.104620",
pages = "104620"
}

Taso, E., Stefanović, V., Gaudin, A., Grujić, J., Maldonado, E., Petković-Curcin, A., Vojvodić, D., Sculean, A.,& Rakić, M.. (2019). Effect of dental caries on periodontal inflammatory status: A split-mouth study.. in Archives of Oral Biology
Pergamon., 110, 104620.
https://doi.org/10.1016/j.archoralbio.2019.104620

Taso E, Stefanović V, Gaudin A, Grujić J, Maldonado E, Petković-Curcin A, Vojvodić D, Sculean A, Rakić M. Effect of dental caries on periodontal inflammatory status: A split-mouth study.. in Archives of Oral Biology. 2019;110:104620.
doi:10.1016/j.archoralbio.2019.104620 .

Taso, Ervin, Stefanović, Vladimir, Gaudin, Alexis, Grujić, Jovan, Maldonado, Estela, Petković-Curcin, Aleksandra, Vojvodić, Danilo, Sculean, Anton, Rakić, Mia, "Effect of dental caries on periodontal inflammatory status: A split-mouth study." in Archives of Oral Biology, 110 (2019):104620,
https://doi.org/10.1016/j.archoralbio.2019.104620 . .

TY  - JOUR
AU  - Jović, Milena
AU  - Lončarević-Vasiljković, Nataša
AU  - Ivković, Sanja
AU  - Dinić, Jelena
AU  - Milanović, Desanka
AU  - Zloković, Berislav
AU  - Kanazir, Selma
PY  - 2019
UR  - http://dx.plos.org/10.1371/journal.pone.0216726
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6522015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3405
AB  - Dystrophic neurites and activated microglia are one of the main neuropathological characteristics of Alzheimer's disease (AD). Although the use of supplements with omega-3 fatty acids has been associated with reduced risk and lessened AD pathology, it still remains elusive whether such a treatment could affect dystrophic neurites (DNs) formation and microglia/macrophage behavior in the early phase of disease. We analyzed the effects of short-term (3 weeks) fish oil supplementation on DNs formation, tau hyperphosphorylation, Amyloid-beta peptide 1-42 (Aβ42) levels and microglial/macrophage response to AD pathology in the parietal cortex of 4-month-old 5xFAD mice, a mouse model of AD. The present study shows for the first time that short-term FO supplementation applied in presymptomatic stage of AD, alters the behaviour of microglia/macrophages prompting them to establish a physical barrier around amyloid plaques. This barrier significantly suppresses DNs formation through the reduction of both Aβ content and tau hyperphosphorylation. Moreover, the short-term FO treatment neither suppresses inflammation nor enhances phagocytic properties of microglia/macrophages in the response to Aβ pathology, the effects most commonly attributed to the fish oil supplementation. Our findings suggest that fish oil consumption may play an important role in modulating microglial/macrophage response and ameliorating the AD pathology in presymptomatic stage of Alzheimer's disease.
T2  - PloS One
T1  - Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model.
IS  - 5
VL  - 14
DO  - 10.1371/journal.pone.0216726
SP  - e0216726
ER  - 

@article{
author = "Jović, Milena and Lončarević-Vasiljković, Nataša and Ivković, Sanja and Dinić, Jelena and Milanović, Desanka and Zloković, Berislav and Kanazir, Selma",
year = "2019",
abstract = "Dystrophic neurites and activated microglia are one of the main neuropathological characteristics of Alzheimer's disease (AD). Although the use of supplements with omega-3 fatty acids has been associated with reduced risk and lessened AD pathology, it still remains elusive whether such a treatment could affect dystrophic neurites (DNs) formation and microglia/macrophage behavior in the early phase of disease. We analyzed the effects of short-term (3 weeks) fish oil supplementation on DNs formation, tau hyperphosphorylation, Amyloid-beta peptide 1-42 (Aβ42) levels and microglial/macrophage response to AD pathology in the parietal cortex of 4-month-old 5xFAD mice, a mouse model of AD. The present study shows for the first time that short-term FO supplementation applied in presymptomatic stage of AD, alters the behaviour of microglia/macrophages prompting them to establish a physical barrier around amyloid plaques. This barrier significantly suppresses DNs formation through the reduction of both Aβ content and tau hyperphosphorylation. Moreover, the short-term FO treatment neither suppresses inflammation nor enhances phagocytic properties of microglia/macrophages in the response to Aβ pathology, the effects most commonly attributed to the fish oil supplementation. Our findings suggest that fish oil consumption may play an important role in modulating microglial/macrophage response and ameliorating the AD pathology in presymptomatic stage of Alzheimer's disease.",
journal = "PloS One",
title = "Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model.",
number = "5",
volume = "14",
doi = "10.1371/journal.pone.0216726",
pages = "e0216726"
}

Jović, M., Lončarević-Vasiljković, N., Ivković, S., Dinić, J., Milanović, D., Zloković, B.,& Kanazir, S.. (2019). Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model.. in PloS One, 14(5), e0216726.
https://doi.org/10.1371/journal.pone.0216726

Jović M, Lončarević-Vasiljković N, Ivković S, Dinić J, Milanović D, Zloković B, Kanazir S. Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model.. in PloS One. 2019;14(5):e0216726.
doi:10.1371/journal.pone.0216726 .

Jović, Milena, Lončarević-Vasiljković, Nataša, Ivković, Sanja, Dinić, Jelena, Milanović, Desanka, Zloković, Berislav, Kanazir, Selma, "Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model." in PloS One, 14, no. 5 (2019):e0216726,
https://doi.org/10.1371/journal.pone.0216726 . .

TY  - JOUR
AU  - Ćirić, Jelena
AU  - Kapor, Slobodan
AU  - Perović, Milka
AU  - Šaponjić, Jasna
PY  - 2019
UR  - https://www.frontiersin.org/article/10.3389/fnins.2019.00148/full
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6401659
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3294
AB  - Our previous studies in the rat model of Parkinson's disease (PD) cholinopathy demonstrated the sleep-related alterations in electroencephalographic (EEG) oscillations at the cortical and hippocampal levels, cortical drives, and sleep spindles (SSs) as the earliest functional biomarkers preceding hypokinesia. Our aim in this study was to follow the impact of a unilateral substantia nigra pars compacta (SNpc) lesion in rat on the cortical and hippocampal sleep architectures and their EEG microstructures, as well as the cortico-hippocampal synchronizations of EEG oscillations, and the SS and high voltage sleep spindle (HVS) dynamics during NREM and REM sleep. We performed unilateral SNpc lesions using two different concentrations/volumes of 6-hydroxydopamine (6-OHDA; 12 μg/1 μl or 12 μg/2 μl). Whereas the unilateral dopaminergic neuronal loss >50% throughout the overall SNpc rostro-caudal dimension prolonged the Wake state, with no change in the NREM or REM duration, there was a long-lasting theta amplitude augmentation across all sleep states in the motor cortex (MCx), but also in the CA1 hippocampus (Hipp) during both Wake and REM sleep. We demonstrate that SS are the hallmarks of NREM sleep, but that they also occur during REM sleep in the MCx and Hipp of the control rats. Whereas SS are always longer in REM vs. NREM sleep in both structures, they are consistently slower in the Hipp. The dopaminergic neuronal loss increased the density of SS in both structures and shortened them in the MCx during NREM sleep, without changing the intrinsic frequency. Conversely, HVS are the hallmarks of REM sleep in the control rats, slower in the Hipp vs. MCx, and the dopaminergic neuronal loss increased their density in the MCx, but shortened them more consistently in the Hipp during REM sleep. In addition, there was an altered synchronization of the EEG oscillations between the MCx and Hipp in different sleep states, particularly the theta and sigma coherences during REM sleep. We provide novel evidence for the importance of the SNpc dopaminergic innervation in sleep regulation, theta rhythm generation, and SS/HVS dynamics control. We suggest the importance of the underlying REM sleep regulatory substrate to HVS generation and duration and to the cortico-hippocampal synchronizations of EEG oscillations in hemiparkinsonian rats.
T2  - Frontiers in Neuroscience
T1  - Alterations of Sleep and Sleep Oscillations in the Hemiparkinsonian Rat.
VL  - 13
DO  - 10.3389/fnins.2019.00148
SP  - 148
ER  - 

@article{
author = "Ćirić, Jelena and Kapor, Slobodan and Perović, Milka and Šaponjić, Jasna",
year = "2019",
abstract = "Our previous studies in the rat model of Parkinson's disease (PD) cholinopathy demonstrated the sleep-related alterations in electroencephalographic (EEG) oscillations at the cortical and hippocampal levels, cortical drives, and sleep spindles (SSs) as the earliest functional biomarkers preceding hypokinesia. Our aim in this study was to follow the impact of a unilateral substantia nigra pars compacta (SNpc) lesion in rat on the cortical and hippocampal sleep architectures and their EEG microstructures, as well as the cortico-hippocampal synchronizations of EEG oscillations, and the SS and high voltage sleep spindle (HVS) dynamics during NREM and REM sleep. We performed unilateral SNpc lesions using two different concentrations/volumes of 6-hydroxydopamine (6-OHDA; 12 μg/1 μl or 12 μg/2 μl). Whereas the unilateral dopaminergic neuronal loss >50% throughout the overall SNpc rostro-caudal dimension prolonged the Wake state, with no change in the NREM or REM duration, there was a long-lasting theta amplitude augmentation across all sleep states in the motor cortex (MCx), but also in the CA1 hippocampus (Hipp) during both Wake and REM sleep. We demonstrate that SS are the hallmarks of NREM sleep, but that they also occur during REM sleep in the MCx and Hipp of the control rats. Whereas SS are always longer in REM vs. NREM sleep in both structures, they are consistently slower in the Hipp. The dopaminergic neuronal loss increased the density of SS in both structures and shortened them in the MCx during NREM sleep, without changing the intrinsic frequency. Conversely, HVS are the hallmarks of REM sleep in the control rats, slower in the Hipp vs. MCx, and the dopaminergic neuronal loss increased their density in the MCx, but shortened them more consistently in the Hipp during REM sleep. In addition, there was an altered synchronization of the EEG oscillations between the MCx and Hipp in different sleep states, particularly the theta and sigma coherences during REM sleep. We provide novel evidence for the importance of the SNpc dopaminergic innervation in sleep regulation, theta rhythm generation, and SS/HVS dynamics control. We suggest the importance of the underlying REM sleep regulatory substrate to HVS generation and duration and to the cortico-hippocampal synchronizations of EEG oscillations in hemiparkinsonian rats.",
journal = "Frontiers in Neuroscience",
title = "Alterations of Sleep and Sleep Oscillations in the Hemiparkinsonian Rat.",
volume = "13",
doi = "10.3389/fnins.2019.00148",
pages = "148"
}

Ćirić, J., Kapor, S., Perović, M.,& Šaponjić, J.. (2019). Alterations of Sleep and Sleep Oscillations in the Hemiparkinsonian Rat.. in Frontiers in Neuroscience, 13, 148.
https://doi.org/10.3389/fnins.2019.00148

Ćirić J, Kapor S, Perović M, Šaponjić J. Alterations of Sleep and Sleep Oscillations in the Hemiparkinsonian Rat.. in Frontiers in Neuroscience. 2019;13:148.
doi:10.3389/fnins.2019.00148 .

Ćirić, Jelena, Kapor, Slobodan, Perović, Milka, Šaponjić, Jasna, "Alterations of Sleep and Sleep Oscillations in the Hemiparkinsonian Rat." in Frontiers in Neuroscience, 13 (2019):148,
https://doi.org/10.3389/fnins.2019.00148 . .

TY  - THES
AU  - Pavković, Željko
PY  - 2018
UR  - http://uvidok.rcub.bg.ac.rs/handle/123456789/2787
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3137
AB  - Propofol je često korišćeni anestetik u modernoj medicini. Adiktivni potencijal propofola je uočen, kao i uticaj na memorijski proces. Međutim, oba fenomena su još uvek nedovoljno istražena. Imajući u vidu da je adolescencija period izuzetne osetljivosti na dejstvo adiktivnih supstanci i intenzivne maturacije mnemoničkog potencijala, cilj ovog rada je bio da se ispita uticaj jednokratnog izlaganja propofolskoj anesteziji, što je tipičan način kliničke primene anestetika, na dopaminsku signalizaciju, sinaptičku i neuronsku aktivnost u različitim regionima mozga i ponašanje juvenilnih/peripubertetskih pacova, kao model sistema humanog periadolescentnog razvoja. Efekti su analizirani 4, 24 i 48 sati nakon tretamana, kod mužjaka Wistar pacova starih 35 dana. Dobijeni rezultati su po prvi put ukazali da izlaganje propofolskoj anesteziji izaziva promene u ekspresiji/fosforilaciji signalnih molekula koji su već prepoznati kao značajni za dejstvo adiktivnih supstanci. Od svih analiziranih dopaminoceptivnih moždanih regiona (medijalni prefrontalni korteks, strijatum i talamus) jedino su u talamusu uočene značajne promene u ekspresiji fosforilisane/aktivirane forme DARPP-32 proteina, pokazatelja postsinaptičke dopaminske signalizacije, 4 i 24 sata nakon tretmana, i bile su praćene povećanom ekspresijom FosB/ΔFosB proteina, biohemijskog pokazatelja neuronske aktivnosti. Promene su lokalizovane u paraventrikularnom talamičkom jedru i mediodorzalnom talamusu. U strijatumu i medijalnom prefrontalnom korteksu je uočen porast u ekspresiji fosforilisane forme CaMKIIα, biohemijskog senzora sinaptičke aktivnosti koji ima važnu ulogu u pamćenju prethodnog izlaganja adiktivnim supstancama. Smanjenje u intenzitetu anksioznosti (procenjeno na osnovu rezultata dobijenih u testu svetlo/tamne kutije i uzdignutog krstastog lavirinta) je zabeleženo 24 sata nakon tretmana, kada je uočen i pad u ekspresiji FosB proteina u strijatumu, što se može tumačiti kao traženje senzacija usled smanjene aktivnosti moždanog regiona značajnog za osećaj zadovoljstva i motivisanost. Pojačan motorički odgovor na d-amfetamin i fenciklidin je uočen 24 sata nakon tretmana (ukrštena senzitizacija), kao potvrda da bez obzira na različite primarne mehanizme dejstva propofol i dve korišćene droge koriste iste neuronske puteve za ostvarivanje psihomotoričkih efekata. Rezultati studije su takođe ukazali da kod peripubertetskih pacova nakon izlaganja propofolskoj anesteziji postoje izvesne poteškoće u pozivanju memorije i memorisanju novih informacija u neaverzivnim memorijskim testovima (prostorna habituacija, prepoznavanje novog objekta), 24 sata nakon tretmana. Ove posledice su bile praćene promenama u ekspresiji molekula koji učestvuju u pozivanju i rekonsolidaciji epizodične memorije (BDNF/TrkB, Egr-1, ERK1/2, CaMKIIα, FosB/ΔFosB), u dorzalnom hipokampusu. Uočene poteškoće u prepoznavanju novine su u skladu sa malobrojnim kliničkim studijama, koje naglašavaju značaj kontrole osnovnih kognitivnih funkcija kod starije dece nakon izlaganja propofolskoj anesteziji. Takođe, u svim ispitivanim moždanim regionima osim u talamusu je zabeležen porast u ekspresiji fosforilisane forme Aducinβ proteina, što je indikacija za destabilizaciju citoskeleta i sinaptičku reorganizaciju. Gledano u celini, rezultati ove studije su ukazali da bolje razumevanje bioloških posledica primene propofola u juvenilnom/pubertetskom uzrastu može doprineti sagledavanju starosno zavisnih zdravstvenih rizika tretmana, koji su do sada intenzivno istraživani samo u ekstremima životne dobi, tj. u ranoj postnatalnoj i kasnoj životnoj fazi.
AB  - Propofol is a commonly used anesthetic in modern medicine. Addictive potential of propofol is observed, as well as the impact on the memory process. However, both phenomena are still insufficiently explored. Bearing in mind that adolescence is a period of extreme sensitivity to addictive substances and intense maturation of the mnemonic potential, the aim of this study was to examine the effect of a single exposure to propofol anesthesia, which is a typical method of its clinical application, on dopaminergic signaling, synaptic and neuronal activity in different brain regions and behavior of juvenile/peripubertal rats, as a model system of human periadolescencent development. The effects were analyzed 4, 24 and 48 hours after the treatment, in male Wistar rats aged 35 days.
The obtained findings for the first time showed that exposure to propofol anesthesia caused changes in the expression/phosphorylation of signal molecules that are already recognized as significant for the action of the addictive substances. Of all the analyzed dopaminoceptive brain regions (medial prefrontal cortex, striatum and thalamus), significant changes in the expression of the phosphorylated/activated form of DARPP-32 protein, indicator of postsynaptic dopaminergic signalling, were observed only in the thalamus, 4 and 24 hours after the treatment, and were accompanied by increased expression of FosB/ΔFosB protein, a biochemical indicator of neuronal activity. The alterations were localized in the paraventricular thalamic nucleus and the mid-dorsal thalamus. An increase in the expression of the phosphorylated form of CaMKIIα, a biochemical sensor of synaptic activity that has an important role in memory on addictive substances exposure, was detected in striatum and medial prefrontal cortex. Reduction in the intensity of anxiety (estimated in accordence to the data obtained in the light/dark box and elevated plus maze tests) was observed 24 hours after the treatment, along with the decrease in the expression of FosB protein in striatum, which can be interpreted as a sensation seeking due to decreased activity of brain region important for a pleasure/motivation. An enhanced motor response to d-amphetamine and phencyclidine was observed 24 hours after the treatment (cross
sensitization), as confirmation that despite the different primary mechanisms of action, propofol and these two drugs use the same neuronal pathways to achieve psychomotor effects. The results of the study also indicated that in peripubertal rats exposed to propofol anesthesia, there were some difficulties in memory retrieval and acquisition of new learning in non-aversive memory tests (spatial habituation, novel object recognition), 24 hours after the treatment. These effects were accompanied by changes in the expression of molecules involved in retrieval and reconsolidation of episodic memory (BDNF/TrkB, Egr-1, ERK1/2, CaMKIIα, FosB/ΔFosB) in the dorsal hippocampus. Detected difficulties in recognizing the novelty are consistent with a few clinical studies that emphasize the importance of controlling basic cognitive functions in older children after exposure to propofol anesthesia. Also, in all investigated brain regions, except the thalamus, an increase in the expression of the phosphorylated form of Adducinβ protein was observed, which is an indication of the cytoskelet destabilization and synaptic reorganization.
Overall, the results of this study accentuated that a better understanding of the biological consequences of the use of propofol in juvenile/puberty period could contribute to the undestanding of age-dependent health risks of the treatment, which have been extensively investigated so far only at the extremes of age, i.e. during early postnatal period and in aging.
PB  - Belgrade: University of Belgrade, Faculty of Biology
T2  - University of Belgrade, Faculty of Biology
T1  - Efekti anestezije indukovane propofolom na sinaptičku plastičnost, aktivnost dopaminskog sistema i ponašanje juvenilnih pacova
T1  - The effects of propofol induced anesthesia on synaptic plasticity, dopaminergic system activity and behaviour of juvenile rats
SP  - 1
EP  - 156
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3137
ER  - 

@phdthesis{
author = "Pavković, Željko",
year = "2018",
abstract = "Propofol je često korišćeni anestetik u modernoj medicini. Adiktivni potencijal propofola je uočen, kao i uticaj na memorijski proces. Međutim, oba fenomena su još uvek nedovoljno istražena. Imajući u vidu da je adolescencija period izuzetne osetljivosti na dejstvo adiktivnih supstanci i intenzivne maturacije mnemoničkog potencijala, cilj ovog rada je bio da se ispita uticaj jednokratnog izlaganja propofolskoj anesteziji, što je tipičan način kliničke primene anestetika, na dopaminsku signalizaciju, sinaptičku i neuronsku aktivnost u različitim regionima mozga i ponašanje juvenilnih/peripubertetskih pacova, kao model sistema humanog periadolescentnog razvoja. Efekti su analizirani 4, 24 i 48 sati nakon tretamana, kod mužjaka Wistar pacova starih 35 dana. Dobijeni rezultati su po prvi put ukazali da izlaganje propofolskoj anesteziji izaziva promene u ekspresiji/fosforilaciji signalnih molekula koji su već prepoznati kao značajni za dejstvo adiktivnih supstanci. Od svih analiziranih dopaminoceptivnih moždanih regiona (medijalni prefrontalni korteks, strijatum i talamus) jedino su u talamusu uočene značajne promene u ekspresiji fosforilisane/aktivirane forme DARPP-32 proteina, pokazatelja postsinaptičke dopaminske signalizacije, 4 i 24 sata nakon tretmana, i bile su praćene povećanom ekspresijom FosB/ΔFosB proteina, biohemijskog pokazatelja neuronske aktivnosti. Promene su lokalizovane u paraventrikularnom talamičkom jedru i mediodorzalnom talamusu. U strijatumu i medijalnom prefrontalnom korteksu je uočen porast u ekspresiji fosforilisane forme CaMKIIα, biohemijskog senzora sinaptičke aktivnosti koji ima važnu ulogu u pamćenju prethodnog izlaganja adiktivnim supstancama. Smanjenje u intenzitetu anksioznosti (procenjeno na osnovu rezultata dobijenih u testu svetlo/tamne kutije i uzdignutog krstastog lavirinta) je zabeleženo 24 sata nakon tretmana, kada je uočen i pad u ekspresiji FosB proteina u strijatumu, što se može tumačiti kao traženje senzacija usled smanjene aktivnosti moždanog regiona značajnog za osećaj zadovoljstva i motivisanost. Pojačan motorički odgovor na d-amfetamin i fenciklidin je uočen 24 sata nakon tretmana (ukrštena senzitizacija), kao potvrda da bez obzira na različite primarne mehanizme dejstva propofol i dve korišćene droge koriste iste neuronske puteve za ostvarivanje psihomotoričkih efekata. Rezultati studije su takođe ukazali da kod peripubertetskih pacova nakon izlaganja propofolskoj anesteziji postoje izvesne poteškoće u pozivanju memorije i memorisanju novih informacija u neaverzivnim memorijskim testovima (prostorna habituacija, prepoznavanje novog objekta), 24 sata nakon tretmana. Ove posledice su bile praćene promenama u ekspresiji molekula koji učestvuju u pozivanju i rekonsolidaciji epizodične memorije (BDNF/TrkB, Egr-1, ERK1/2, CaMKIIα, FosB/ΔFosB), u dorzalnom hipokampusu. Uočene poteškoće u prepoznavanju novine su u skladu sa malobrojnim kliničkim studijama, koje naglašavaju značaj kontrole osnovnih kognitivnih funkcija kod starije dece nakon izlaganja propofolskoj anesteziji. Takođe, u svim ispitivanim moždanim regionima osim u talamusu je zabeležen porast u ekspresiji fosforilisane forme Aducinβ proteina, što je indikacija za destabilizaciju citoskeleta i sinaptičku reorganizaciju. Gledano u celini, rezultati ove studije su ukazali da bolje razumevanje bioloških posledica primene propofola u juvenilnom/pubertetskom uzrastu može doprineti sagledavanju starosno zavisnih zdravstvenih rizika tretmana, koji su do sada intenzivno istraživani samo u ekstremima životne dobi, tj. u ranoj postnatalnoj i kasnoj životnoj fazi., Propofol is a commonly used anesthetic in modern medicine. Addictive potential of propofol is observed, as well as the impact on the memory process. However, both phenomena are still insufficiently explored. Bearing in mind that adolescence is a period of extreme sensitivity to addictive substances and intense maturation of the mnemonic potential, the aim of this study was to examine the effect of a single exposure to propofol anesthesia, which is a typical method of its clinical application, on dopaminergic signaling, synaptic and neuronal activity in different brain regions and behavior of juvenile/peripubertal rats, as a model system of human periadolescencent development. The effects were analyzed 4, 24 and 48 hours after the treatment, in male Wistar rats aged 35 days.
The obtained findings for the first time showed that exposure to propofol anesthesia caused changes in the expression/phosphorylation of signal molecules that are already recognized as significant for the action of the addictive substances. Of all the analyzed dopaminoceptive brain regions (medial prefrontal cortex, striatum and thalamus), significant changes in the expression of the phosphorylated/activated form of DARPP-32 protein, indicator of postsynaptic dopaminergic signalling, were observed only in the thalamus, 4 and 24 hours after the treatment, and were accompanied by increased expression of FosB/ΔFosB protein, a biochemical indicator of neuronal activity. The alterations were localized in the paraventricular thalamic nucleus and the mid-dorsal thalamus. An increase in the expression of the phosphorylated form of CaMKIIα, a biochemical sensor of synaptic activity that has an important role in memory on addictive substances exposure, was detected in striatum and medial prefrontal cortex. Reduction in the intensity of anxiety (estimated in accordence to the data obtained in the light/dark box and elevated plus maze tests) was observed 24 hours after the treatment, along with the decrease in the expression of FosB protein in striatum, which can be interpreted as a sensation seeking due to decreased activity of brain region important for a pleasure/motivation. An enhanced motor response to d-amphetamine and phencyclidine was observed 24 hours after the treatment (cross
sensitization), as confirmation that despite the different primary mechanisms of action, propofol and these two drugs use the same neuronal pathways to achieve psychomotor effects. The results of the study also indicated that in peripubertal rats exposed to propofol anesthesia, there were some difficulties in memory retrieval and acquisition of new learning in non-aversive memory tests (spatial habituation, novel object recognition), 24 hours after the treatment. These effects were accompanied by changes in the expression of molecules involved in retrieval and reconsolidation of episodic memory (BDNF/TrkB, Egr-1, ERK1/2, CaMKIIα, FosB/ΔFosB) in the dorsal hippocampus. Detected difficulties in recognizing the novelty are consistent with a few clinical studies that emphasize the importance of controlling basic cognitive functions in older children after exposure to propofol anesthesia. Also, in all investigated brain regions, except the thalamus, an increase in the expression of the phosphorylated form of Adducinβ protein was observed, which is an indication of the cytoskelet destabilization and synaptic reorganization.
Overall, the results of this study accentuated that a better understanding of the biological consequences of the use of propofol in juvenile/puberty period could contribute to the undestanding of age-dependent health risks of the treatment, which have been extensively investigated so far only at the extremes of age, i.e. during early postnatal period and in aging.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "Efekti anestezije indukovane propofolom na sinaptičku plastičnost, aktivnost dopaminskog sistema i ponašanje juvenilnih pacova, The effects of propofol induced anesthesia on synaptic plasticity, dopaminergic system activity and behaviour of juvenile rats",
pages = "1-156",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3137"
}

Pavković, Ž.. (2018). Efekti anestezije indukovane propofolom na sinaptičku plastičnost, aktivnost dopaminskog sistema i ponašanje juvenilnih pacova. in University of Belgrade, Faculty of Biology
Belgrade: University of Belgrade, Faculty of Biology., 1-156.
https://hdl.handle.net/21.15107/rcub_ibiss_3137

Pavković Ž. Efekti anestezije indukovane propofolom na sinaptičku plastičnost, aktivnost dopaminskog sistema i ponašanje juvenilnih pacova. in University of Belgrade, Faculty of Biology. 2018;:1-156.
https://hdl.handle.net/21.15107/rcub_ibiss_3137 .

Pavković, Željko, "Efekti anestezije indukovane propofolom na sinaptičku plastičnost, aktivnost dopaminskog sistema i ponašanje juvenilnih pacova" in University of Belgrade, Faculty of Biology (2018):1-156,
https://hdl.handle.net/21.15107/rcub_ibiss_3137 .

TY  - JOUR
AU  - Ćirić, Jelena
AU  - Lazić, Katarina
AU  - Kapor, Slobodan
AU  - Perović, Milka
AU  - Petrović, Jelena
AU  - Pešić, Vesna
AU  - Kanazir, Selma
AU  - Šaponjić, Jasna
PY  - 2018
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0166432817312391
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29170000
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2932
AB  - In order to find out the possible earliest biomarkers of Parkinson's disease (PD) cholinopathy, we followed the impact of bilateral pedunculopontine tegmental nucleus (PPT) lesion in rat on: the cortical and hippocampal sleep/wake states architectures, all sleep states related EEG microstructures, sleep spindles, the basal and stimulated locomotor activity. Sleep and basal locomotor activity in adult Wistar rats were followed during their inactive circadian phase, and throughout the same aging period. The bilateral PPT lesions were done by 0.1M ibotenic acid (IBO) during the surgical procedure for implantation of the electroencephalographic (EEG) and electromyographic (EMG) electrodes for chronic sleep recording. The cholinergic neuronal loss was identified by NADPH - diaphorase histochemistry. After all sleep and behavioral recording sessions, the locomotor activity was stimulated by d-amphetamine (d-AMPH) and the neuronal activity of striatum was followed by c-Fos immunolabeling. Impaired cholinergic innervation from the PPT was expressed earlier as sleep disorder then as movement disorder, and it was the earliest and long-lasting at hippocampal and thalamo-cortical level, and followed by a delayed "hypokinesia". This severe impact of a tonically impaired PPT cholinergic innervation was evidenced as the cholinergic interneuronal loss of the caudate putamen and as a suppressed c-Fos expression after stimulation by d-AMPH. In order how they occurred, the hippocampal non rapid eye movement (NREM) sleep disorder, altered high voltage sleep spindle (HVS) dynamics during rapid eye movement (REM) sleep in the hippocampus and motor cortex, and "hypokinesia" may serve as the biomarkers of PD cholinopathy onset and progression.
T2  - Behavioural Brain Research
T1  - Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat
VL  - 339
DO  - 10.1016/j.bbr.2017.11.021
SP  - 79
EP  - 92
ER  - 

@article{
author = "Ćirić, Jelena and Lazić, Katarina and Kapor, Slobodan and Perović, Milka and Petrović, Jelena and Pešić, Vesna and Kanazir, Selma and Šaponjić, Jasna",
year = "2018",
abstract = "In order to find out the possible earliest biomarkers of Parkinson's disease (PD) cholinopathy, we followed the impact of bilateral pedunculopontine tegmental nucleus (PPT) lesion in rat on: the cortical and hippocampal sleep/wake states architectures, all sleep states related EEG microstructures, sleep spindles, the basal and stimulated locomotor activity. Sleep and basal locomotor activity in adult Wistar rats were followed during their inactive circadian phase, and throughout the same aging period. The bilateral PPT lesions were done by 0.1M ibotenic acid (IBO) during the surgical procedure for implantation of the electroencephalographic (EEG) and electromyographic (EMG) electrodes for chronic sleep recording. The cholinergic neuronal loss was identified by NADPH - diaphorase histochemistry. After all sleep and behavioral recording sessions, the locomotor activity was stimulated by d-amphetamine (d-AMPH) and the neuronal activity of striatum was followed by c-Fos immunolabeling. Impaired cholinergic innervation from the PPT was expressed earlier as sleep disorder then as movement disorder, and it was the earliest and long-lasting at hippocampal and thalamo-cortical level, and followed by a delayed "hypokinesia". This severe impact of a tonically impaired PPT cholinergic innervation was evidenced as the cholinergic interneuronal loss of the caudate putamen and as a suppressed c-Fos expression after stimulation by d-AMPH. In order how they occurred, the hippocampal non rapid eye movement (NREM) sleep disorder, altered high voltage sleep spindle (HVS) dynamics during rapid eye movement (REM) sleep in the hippocampus and motor cortex, and "hypokinesia" may serve as the biomarkers of PD cholinopathy onset and progression.",
journal = "Behavioural Brain Research",
title = "Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat",
volume = "339",
doi = "10.1016/j.bbr.2017.11.021",
pages = "79-92"
}

Ćirić, J., Lazić, K., Kapor, S., Perović, M., Petrović, J., Pešić, V., Kanazir, S.,& Šaponjić, J.. (2018). Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat. in Behavioural Brain Research, 339, 79-92.
https://doi.org/10.1016/j.bbr.2017.11.021

Ćirić J, Lazić K, Kapor S, Perović M, Petrović J, Pešić V, Kanazir S, Šaponjić J. Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat. in Behavioural Brain Research. 2018;339:79-92.
doi:10.1016/j.bbr.2017.11.021 .

Ćirić, Jelena, Lazić, Katarina, Kapor, Slobodan, Perović, Milka, Petrović, Jelena, Pešić, Vesna, Kanazir, Selma, Šaponjić, Jasna, "Sleep disorder and altered locomotor activity as biomarkers of the Parkinson's disease cholinopathy in rat" in Behavioural Brain Research, 339 (2018):79-92,
https://doi.org/10.1016/j.bbr.2017.11.021 . .

TY  - CONF
AU  - Jović, Milena
AU  - Lončarević-Vasiljković, Nataša
AU  - Ivković, Sanja
AU  - Milanović, Desanka
AU  - Avramović, Vladimir
AU  - Kanazir, Selma
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5719
AB  - Defining features of Alzheimer's disease (AD) pathology are the formation of amyloid plaques, neurofibrillary tangles, neuron loss and inflammation. Plaques are encircled by a halo of diffuse Aβ, surrounded by dystrophic neurites (DNs) and activated glia. High level of Aβ suppresses microglial ability to clear Aβ and activate inflammatory response that becomes neurotoxic. These microglial cells become dysfunctional and can further contribute to AD pathology. 

We investigated the influence of omega-3 fatty acids, the main compounds of fish oil (FO), on Aβ load, neuritic dystrophy and behavior of microglial cells in parietal cortex in 5xFAD mice. 

Three-month old female 5xFAD mice received FO (100μl/animal/day) via oral gavage during 3 weeks period. Aβ-pathology was visualized immunohistochemically. We used ThioflavinS and AmiloGlo to visualize plaques, anti-Aβ42 antibody for soluble Aβ peptide labeling, anti-SMI31 antibody for neuritic dystrophy and anti-Iba-1 antibody for microglial cells. Immunostaining was observed by confocal microscopy. Quantification was done by Image J program. 

Our results showed that short-term FO supplementation was capable of: (i) inducing significant decreased of total Aβ levels (ii) preventing the emergence of neuritic dystrophy in parietal cortex of 5xFAD mice; (iii) increasing overall microglial number; and (iv) enhancing clustering of microglial cells around amyloid plaques, representing mechanical barrier that prevents further Aβ  aggregation. 

This study represents valuable contribution to better biological understanding how FO suppresses AD pathology through typical pleiotropic effect. We believe that FO in combination with other drugs could be good approach for long-term treatment in slowing down AD pathology.
PB  - Brussels, Belgium: Federation of European Neurocience Societies
C3  - 11th FENS Forum of Neuroscience; 2018 Jul 7-11; Berlin, Germany
T1  - Influence of fish oil treatment on microglial cell behavior and Aβ-like pathology in 5xFAD mice model of Alzheimer’s disease
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5719
ER  - 

@conference{
author = "Jović, Milena and Lončarević-Vasiljković, Nataša and Ivković, Sanja and Milanović, Desanka and Avramović, Vladimir and Kanazir, Selma",
year = "2018",
abstract = "Defining features of Alzheimer's disease (AD) pathology are the formation of amyloid plaques, neurofibrillary tangles, neuron loss and inflammation. Plaques are encircled by a halo of diffuse Aβ, surrounded by dystrophic neurites (DNs) and activated glia. High level of Aβ suppresses microglial ability to clear Aβ and activate inflammatory response that becomes neurotoxic. These microglial cells become dysfunctional and can further contribute to AD pathology. 

We investigated the influence of omega-3 fatty acids, the main compounds of fish oil (FO), on Aβ load, neuritic dystrophy and behavior of microglial cells in parietal cortex in 5xFAD mice. 

Three-month old female 5xFAD mice received FO (100μl/animal/day) via oral gavage during 3 weeks period. Aβ-pathology was visualized immunohistochemically. We used ThioflavinS and AmiloGlo to visualize plaques, anti-Aβ42 antibody for soluble Aβ peptide labeling, anti-SMI31 antibody for neuritic dystrophy and anti-Iba-1 antibody for microglial cells. Immunostaining was observed by confocal microscopy. Quantification was done by Image J program. 

Our results showed that short-term FO supplementation was capable of: (i) inducing significant decreased of total Aβ levels (ii) preventing the emergence of neuritic dystrophy in parietal cortex of 5xFAD mice; (iii) increasing overall microglial number; and (iv) enhancing clustering of microglial cells around amyloid plaques, representing mechanical barrier that prevents further Aβ  aggregation. 

This study represents valuable contribution to better biological understanding how FO suppresses AD pathology through typical pleiotropic effect. We believe that FO in combination with other drugs could be good approach for long-term treatment in slowing down AD pathology.",
publisher = "Brussels, Belgium: Federation of European Neurocience Societies",
journal = "11th FENS Forum of Neuroscience; 2018 Jul 7-11; Berlin, Germany",
title = "Influence of fish oil treatment on microglial cell behavior and Aβ-like pathology in 5xFAD mice model of Alzheimer’s disease",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5719"
}

Jović, M., Lončarević-Vasiljković, N., Ivković, S., Milanović, D., Avramović, V.,& Kanazir, S.. (2018). Influence of fish oil treatment on microglial cell behavior and Aβ-like pathology in 5xFAD mice model of Alzheimer’s disease. in 11th FENS Forum of Neuroscience; 2018 Jul 7-11; Berlin, Germany
Brussels, Belgium: Federation of European Neurocience Societies..
https://hdl.handle.net/21.15107/rcub_ibiss_5719

Jović M, Lončarević-Vasiljković N, Ivković S, Milanović D, Avramović V, Kanazir S. Influence of fish oil treatment on microglial cell behavior and Aβ-like pathology in 5xFAD mice model of Alzheimer’s disease. in 11th FENS Forum of Neuroscience; 2018 Jul 7-11; Berlin, Germany. 2018;.
https://hdl.handle.net/21.15107/rcub_ibiss_5719 .

Jović, Milena, Lončarević-Vasiljković, Nataša, Ivković, Sanja, Milanović, Desanka, Avramović, Vladimir, Kanazir, Selma, "Influence of fish oil treatment on microglial cell behavior and Aβ-like pathology in 5xFAD mice model of Alzheimer’s disease" in 11th FENS Forum of Neuroscience; 2018 Jul 7-11; Berlin, Germany (2018),
https://hdl.handle.net/21.15107/rcub_ibiss_5719 .