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  - 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 .

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/123456789/5716
AB  - Dystrophic neurites (DNs) and activated microglia are one of the neuropathological characteristics of Alzheimer's disease (AD). Although the use of supplements with omega-3 (0) fatty acids has been associated with reduced risk and lessened. AD pathology, it still remains elusive whether such a treatment could affect DNs formation and microglia behavior in the early phase of disease. We examined influence of fish oil treatment on pathological hallmarks in the brain of 5xFAD mice which rapidly recapitulate major hallmarks of AD amyloid pathology. Three-month old female 5xFAD mice received FO (10011.1/animal/day) via oral Savage during 3 weeks period. Histological analysis was used to detect changes in pathological features of AD in parietal cortex in 5xFAD mice. ThioflavinS and AmiloGlo were used to visualize plaques. Soluble Ap peptide, neuritic dystrophy and microglial cells were detect by anti-A1342-, anti-SMI31- and anti-Iba-1- antibodies, retrospectively. Immunostaining was observed by confocal microscopy. Quantification was done by Image J program. Our results showed that short-term FO supplementation is capable of inducing significant decreased of total Ap levels and preventing the emergence of neuritic dystrophy in parietal cortex of 5xFAD mice. FO supplementation led to increase in overall microglial number and enhanced clustering of microglial cells around amyloid plaques, representing mechanical barrier that doesn't allow AP to aggregate. These results confirmed and extended previous findings suggesting that FO suppresses brain aging and has a typical pleiotropic effect. We believe that FO in combination with other drugs could be good approach for long-term treatment in AD suppression.
PB  - FEBS Balaton 2018
C3  - Final Programme and Book of Abstracts: FEBS3+: From molecules to living systems; 2018 Sep 2-5; Siofok, Hungary
T1  - Influence of fish oil treatment on microglial cell behavior and dystrophic neurites in 5XFAD mice model of Alzheimer's disease
SP  - P8-03
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5716
ER  - 

@conference{
author = "Jović, Milena and Lončarević-Vasiljković, Nataša and Ivković, Sanja and Milanović, Desanka and Avramović, Vladimir and Kanazir, Selma",
year = "2018",
abstract = "Dystrophic neurites (DNs) and activated microglia are one of the neuropathological characteristics of Alzheimer's disease (AD). Although the use of supplements with omega-3 (0) fatty acids has been associated with reduced risk and lessened. AD pathology, it still remains elusive whether such a treatment could affect DNs formation and microglia behavior in the early phase of disease. We examined influence of fish oil treatment on pathological hallmarks in the brain of 5xFAD mice which rapidly recapitulate major hallmarks of AD amyloid pathology. Three-month old female 5xFAD mice received FO (10011.1/animal/day) via oral Savage during 3 weeks period. Histological analysis was used to detect changes in pathological features of AD in parietal cortex in 5xFAD mice. ThioflavinS and AmiloGlo were used to visualize plaques. Soluble Ap peptide, neuritic dystrophy and microglial cells were detect by anti-A1342-, anti-SMI31- and anti-Iba-1- antibodies, retrospectively. Immunostaining was observed by confocal microscopy. Quantification was done by Image J program. Our results showed that short-term FO supplementation is capable of inducing significant decreased of total Ap levels and preventing the emergence of neuritic dystrophy in parietal cortex of 5xFAD mice. FO supplementation led to increase in overall microglial number and enhanced clustering of microglial cells around amyloid plaques, representing mechanical barrier that doesn't allow AP to aggregate. These results confirmed and extended previous findings suggesting that FO suppresses brain aging and has a typical pleiotropic effect. We believe that FO in combination with other drugs could be good approach for long-term treatment in AD suppression.",
publisher = "FEBS Balaton 2018",
journal = "Final Programme and Book of Abstracts: FEBS3+: From molecules to living systems; 2018 Sep 2-5; Siofok, Hungary",
title = "Influence of fish oil treatment on microglial cell behavior and dystrophic neurites in 5XFAD mice model of Alzheimer's disease",
pages = "P8-03",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5716"
}

Jović, M., Lončarević-Vasiljković, N., Ivković, S., Milanović, D., Avramović, V.,& Kanazir, S.. (2018). Influence of fish oil treatment on microglial cell behavior and dystrophic neurites in 5XFAD mice model of Alzheimer's disease. in Final Programme and Book of Abstracts: FEBS3+: From molecules to living systems; 2018 Sep 2-5; Siofok, Hungary
FEBS Balaton 2018., P8-03.
https://hdl.handle.net/21.15107/rcub_ibiss_5716

Jović M, Lončarević-Vasiljković N, Ivković S, Milanović D, Avramović V, Kanazir S. Influence of fish oil treatment on microglial cell behavior and dystrophic neurites in 5XFAD mice model of Alzheimer's disease. in Final Programme and Book of Abstracts: FEBS3+: From molecules to living systems; 2018 Sep 2-5; Siofok, Hungary. 2018;:P8-03.
https://hdl.handle.net/21.15107/rcub_ibiss_5716 .

Jović, Milena, Lončarević-Vasiljković, Nataša, Ivković, Sanja, Milanović, Desanka, Avramović, Vladimir, Kanazir, Selma, "Influence of fish oil treatment on microglial cell behavior and dystrophic neurites in 5XFAD mice model of Alzheimer's disease" in Final Programme and Book of Abstracts: FEBS3+: From molecules to living systems; 2018 Sep 2-5; Siofok, Hungary (2018):P8-03,
https://hdl.handle.net/21.15107/rcub_ibiss_5716 .

TY  - JOUR
AU  - Milanović, Desanka
AU  - Petrovic, Snjezana
AU  - Brkić, Marjana
AU  - Avramović, Vladimir
AU  - Perović, Milka
AU  - Ivković, Sanja
AU  - Glibetić, Marija
AU  - Kanazir, Selma
PY  - 2018
UR  - http://www.mdpi.com/2072-6643/10/9/1250
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3136
AB  - Long-term fish oil (FO) supplementation is able to improve Alzheimer's disease (AD) pathology. We aimed to determine the impact of short-term fish oil (FO) intake on phospholipids composition and plaque pathology in 5xFAD mice, a widely used animal model of AD. A 3-week-long FO supplementation administered at 3 months of age decreased the number of dense core plaques in the 5xFAD cortex and changed phospholipids in the livers and brains of wild-type (Wt) and 5xFAD mice. Livers of both genotypes responded by increase of n-3 and reciprocal decrease of n-6 fatty acids. In Wt brains, FO supplementation induced elevation of n-3 fatty acids and subsequent enhancement of n-6/n-3 ratio. However, in 5xFAD brains the improved n-6/n-3 ratio was mainly due to FO-induced decrease in arachidonic and adrenic n-6 fatty acids. Also, brain and liver abundance of n-3 fatty acids were strongly correlated in Wts, oppositely to 5xFADs where significant brain-liver correlation exists only for n-6 fatty acids. Expression of omega-3 transporter Mfs2a remained unchanged after FO supplementation. We have demonstrated that even a short-term FO intake improves the phospholipid composition and has a significant effect on plaque burden in 5xFAD brains when applied in early stages of AD pathology.
T2  - Nutrients
T1  - Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of the 5xFAD Mouse Model of Alzheimer's Disease.
IS  - 9
VL  - 10
DO  - 10.3390/nu10091250
SP  - 1250
ER  - 

@article{
author = "Milanović, Desanka and Petrovic, Snjezana and Brkić, Marjana and Avramović, Vladimir and Perović, Milka and Ivković, Sanja and Glibetić, Marija and Kanazir, Selma",
year = "2018",
abstract = "Long-term fish oil (FO) supplementation is able to improve Alzheimer's disease (AD) pathology. We aimed to determine the impact of short-term fish oil (FO) intake on phospholipids composition and plaque pathology in 5xFAD mice, a widely used animal model of AD. A 3-week-long FO supplementation administered at 3 months of age decreased the number of dense core plaques in the 5xFAD cortex and changed phospholipids in the livers and brains of wild-type (Wt) and 5xFAD mice. Livers of both genotypes responded by increase of n-3 and reciprocal decrease of n-6 fatty acids. In Wt brains, FO supplementation induced elevation of n-3 fatty acids and subsequent enhancement of n-6/n-3 ratio. However, in 5xFAD brains the improved n-6/n-3 ratio was mainly due to FO-induced decrease in arachidonic and adrenic n-6 fatty acids. Also, brain and liver abundance of n-3 fatty acids were strongly correlated in Wts, oppositely to 5xFADs where significant brain-liver correlation exists only for n-6 fatty acids. Expression of omega-3 transporter Mfs2a remained unchanged after FO supplementation. We have demonstrated that even a short-term FO intake improves the phospholipid composition and has a significant effect on plaque burden in 5xFAD brains when applied in early stages of AD pathology.",
journal = "Nutrients",
title = "Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of the 5xFAD Mouse Model of Alzheimer's Disease.",
number = "9",
volume = "10",
doi = "10.3390/nu10091250",
pages = "1250"
}

Milanović, D., Petrovic, S., Brkić, M., Avramović, V., Perović, M., Ivković, S., Glibetić, M.,& Kanazir, S.. (2018). Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of the 5xFAD Mouse Model of Alzheimer's Disease.. in Nutrients, 10(9), 1250.
https://doi.org/10.3390/nu10091250

Milanović D, Petrovic S, Brkić M, Avramović V, Perović M, Ivković S, Glibetić M, Kanazir S. Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of the 5xFAD Mouse Model of Alzheimer's Disease.. in Nutrients. 2018;10(9):1250.
doi:10.3390/nu10091250 .

Milanović, Desanka, Petrovic, Snjezana, Brkić, Marjana, Avramović, Vladimir, Perović, Milka, Ivković, Sanja, Glibetić, Marija, Kanazir, Selma, "Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of the 5xFAD Mouse Model of Alzheimer's Disease." in Nutrients, 10, no. 9 (2018):1250,
https://doi.org/10.3390/nu10091250 . .

TY  - JOUR
AU  - Milanović, Desanka
AU  - Pešić, Vesna
AU  - Lončarević-Vasiljković, Nataša
AU  - Avramović, Vladimir
AU  - Tešić, Vesna
AU  - Jevtović-Todorović, Vesna
AU  - Kanazir, Selma
AU  - Ruždijić, Sabera
PY  - 2017
UR  - http://link.springer.com/10.1007/s12640-017-9730-0
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2741
AB  - Propofol is a general anesthetic commonly used in pediatric clinical practices. Experimental findings demonstrate that anesthetics induce widespread apoptosis and cognitive decline in a developing brain. Although anesthesia-mediated neurotoxicity is the most prominent during intense period of synaptogenesis, the effects of an early anesthesia exposure on the synapses are not well understood. The aim of this study was to examine the effects of neonatal propofol anesthesia on the expression of key proteins that participate in synaptogenesis and synaptic plasticity and to evaluate long-term neurobehavioral abnormalities in the mature adult brain. Propofol-injected 7-day-old rats were maintained under 2-, 4-, and 6-h-long anesthesia and sacrificed 0, 4, 16, and 24 h after the termination of each exposure. We showed that propofol anesthesia strongly influenced spatiotemporal expression and/or proteolytic processing of crucial presynaptic (GAP-43, synaptophysin, α-synuclein), trans-synaptic (N-cadherin), and postsynaptic (drebrin, MAP-2) proteins in the cortex and thalamus. An overall decrease of synaptophysin, α-synuclein, N-cadherin, and drebrin indicated impaired function and structure of the synaptic contacts immediately after anesthesia cessation. GAP-43 and MAP-2 adult and juvenile isoforms are upregulated following anesthesia, suggesting compensatory mechanism in the maintaining of the structural integrity and stabilization of developing axons and dendritic arbors. Neonatal propofol exposure significantly altered spontaneous motor activity (increased stereotypic/repetitive movements) and changed emotional behavior (reduced anxiety-like response) in the adulthood, 6 months later. These findings suggest that propofol anesthesia is synaptotoxic in the developing brain, disturbing synaptic dynamics and producing neuroplastic changes permanently incorporated into existing networks with long-lasting functional consequences.
T2  - Neurotoxicity Research
T1  - Neonatal Propofol Anesthesia Changes Expression of Synaptic Plasticity Proteins and Increases Stereotypic and Anxyolitic Behavior in Adult Rats
VL  - 32
DO  - 10.1007/s12640-017-9730-0
SP  - 247
EP  - 263
ER  - 

@article{
author = "Milanović, Desanka and Pešić, Vesna and Lončarević-Vasiljković, Nataša and Avramović, Vladimir and Tešić, Vesna and Jevtović-Todorović, Vesna and Kanazir, Selma and Ruždijić, Sabera",
year = "2017",
abstract = "Propofol is a general anesthetic commonly used in pediatric clinical practices. Experimental findings demonstrate that anesthetics induce widespread apoptosis and cognitive decline in a developing brain. Although anesthesia-mediated neurotoxicity is the most prominent during intense period of synaptogenesis, the effects of an early anesthesia exposure on the synapses are not well understood. The aim of this study was to examine the effects of neonatal propofol anesthesia on the expression of key proteins that participate in synaptogenesis and synaptic plasticity and to evaluate long-term neurobehavioral abnormalities in the mature adult brain. Propofol-injected 7-day-old rats were maintained under 2-, 4-, and 6-h-long anesthesia and sacrificed 0, 4, 16, and 24 h after the termination of each exposure. We showed that propofol anesthesia strongly influenced spatiotemporal expression and/or proteolytic processing of crucial presynaptic (GAP-43, synaptophysin, α-synuclein), trans-synaptic (N-cadherin), and postsynaptic (drebrin, MAP-2) proteins in the cortex and thalamus. An overall decrease of synaptophysin, α-synuclein, N-cadherin, and drebrin indicated impaired function and structure of the synaptic contacts immediately after anesthesia cessation. GAP-43 and MAP-2 adult and juvenile isoforms are upregulated following anesthesia, suggesting compensatory mechanism in the maintaining of the structural integrity and stabilization of developing axons and dendritic arbors. Neonatal propofol exposure significantly altered spontaneous motor activity (increased stereotypic/repetitive movements) and changed emotional behavior (reduced anxiety-like response) in the adulthood, 6 months later. These findings suggest that propofol anesthesia is synaptotoxic in the developing brain, disturbing synaptic dynamics and producing neuroplastic changes permanently incorporated into existing networks with long-lasting functional consequences.",
journal = "Neurotoxicity Research",
title = "Neonatal Propofol Anesthesia Changes Expression of Synaptic Plasticity Proteins and Increases Stereotypic and Anxyolitic Behavior in Adult Rats",
volume = "32",
doi = "10.1007/s12640-017-9730-0",
pages = "247-263"
}

Milanović, D., Pešić, V., Lončarević-Vasiljković, N., Avramović, V., Tešić, V., Jevtović-Todorović, V., Kanazir, S.,& Ruždijić, S.. (2017). Neonatal Propofol Anesthesia Changes Expression of Synaptic Plasticity Proteins and Increases Stereotypic and Anxyolitic Behavior in Adult Rats. in Neurotoxicity Research, 32, 247-263.
https://doi.org/10.1007/s12640-017-9730-0

Milanović D, Pešić V, Lončarević-Vasiljković N, Avramović V, Tešić V, Jevtović-Todorović V, Kanazir S, Ruždijić S. Neonatal Propofol Anesthesia Changes Expression of Synaptic Plasticity Proteins and Increases Stereotypic and Anxyolitic Behavior in Adult Rats. in Neurotoxicity Research. 2017;32:247-263.
doi:10.1007/s12640-017-9730-0 .

Milanović, Desanka, Pešić, Vesna, Lončarević-Vasiljković, Nataša, Avramović, Vladimir, Tešić, Vesna, Jevtović-Todorović, Vesna, Kanazir, Selma, Ruždijić, Sabera, "Neonatal Propofol Anesthesia Changes Expression of Synaptic Plasticity Proteins and Increases Stereotypic and Anxyolitic Behavior in Adult Rats" in Neurotoxicity Research, 32 (2017):247-263,
https://doi.org/10.1007/s12640-017-9730-0 . .

TY  - CONF
AU  - Lončarević-Vasiljković, Nataša
AU  - Jović, Milena
AU  - Ivković, Sanja
AU  - Milanović, Desanka
AU  - Dinić, Jelena
AU  - Brkić, Marjana
AU  - Avramović, Vladimir
AU  - Kanazir, Selma
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6001
AB  - Introduction. Dystrophic neurites (DNs) are one of the neuropathological characteristics of Alzheimer's disease (AD) and represent the initial phase of neurodegeneration. Microtubule disruption in presynaptic dystrophic neurites that surround plaques impairs axonal transport and leads to the exacerbation of amyloid pathology in AD. Microglia plays a pivotal role in AD pathology as it is able to constitute a physical barrier around amyloid plaques and limit the accumulation of protofibrilar amyloid beta around the fibrillar plaque core. In such a way microglia can mechanically shield the surrounding neurites from the neurotoxic protofibrillar Aβ aggregates. The use of supplements with omega-3 (ω3) fatty acids (FAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), such as fish oil, is widespread due to proposed beneficial effects on the nervous system. High DHA consumption has been also associated with reduced risk and lessened AD pathology, yet the mechanisms and therapeutic potential  of these supplements remain elusive. Material and Methods. We analyzed the effects of the short-term fish oil (FO) supplementation on 4 months old 5xFAD mice, a mouse model with fast and robust development of the AD pathology hallmarks such as amyloid plaques and dystrophic neurites. Results. We  showed that even the short treatment with FO can affect the microglia clustering around amyloid plaques and increase the microglial plaque envelopment. Consequently, the Aβ accumulation was reduced and the appearance of DNs substantially suppressed. Conclusion. Our findings suggest that increased DHA consumption may play and important role in modulating microglial response and ameliorating AD pathology at least in the early phase of the disease.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia
T1  - The newly discovered effects of fish oil supplementation on AD pathology: What’s next?
SP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6001
ER  - 

@conference{
author = "Lončarević-Vasiljković, Nataša and Jović, Milena and Ivković, Sanja and Milanović, Desanka and Dinić, Jelena and Brkić, Marjana and Avramović, Vladimir and Kanazir, Selma",
year = "2017",
abstract = "Introduction. Dystrophic neurites (DNs) are one of the neuropathological characteristics of Alzheimer's disease (AD) and represent the initial phase of neurodegeneration. Microtubule disruption in presynaptic dystrophic neurites that surround plaques impairs axonal transport and leads to the exacerbation of amyloid pathology in AD. Microglia plays a pivotal role in AD pathology as it is able to constitute a physical barrier around amyloid plaques and limit the accumulation of protofibrilar amyloid beta around the fibrillar plaque core. In such a way microglia can mechanically shield the surrounding neurites from the neurotoxic protofibrillar Aβ aggregates. The use of supplements with omega-3 (ω3) fatty acids (FAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), such as fish oil, is widespread due to proposed beneficial effects on the nervous system. High DHA consumption has been also associated with reduced risk and lessened AD pathology, yet the mechanisms and therapeutic potential  of these supplements remain elusive. Material and Methods. We analyzed the effects of the short-term fish oil (FO) supplementation on 4 months old 5xFAD mice, a mouse model with fast and robust development of the AD pathology hallmarks such as amyloid plaques and dystrophic neurites. Results. We  showed that even the short treatment with FO can affect the microglia clustering around amyloid plaques and increase the microglial plaque envelopment. Consequently, the Aβ accumulation was reduced and the appearance of DNs substantially suppressed. Conclusion. Our findings suggest that increased DHA consumption may play and important role in modulating microglial response and ameliorating AD pathology at least in the early phase of the disease.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia",
title = "The newly discovered effects of fish oil supplementation on AD pathology: What’s next?",
pages = "33",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6001"
}

Lončarević-Vasiljković, N., Jović, M., Ivković, S., Milanović, D., Dinić, J., Brkić, M., Avramović, V.,& Kanazir, S.. (2017). The newly discovered effects of fish oil supplementation on AD pathology: What’s next?. in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 33.
https://hdl.handle.net/21.15107/rcub_ibiss_6001

Lončarević-Vasiljković N, Jović M, Ivković S, Milanović D, Dinić J, Brkić M, Avramović V, Kanazir S. The newly discovered effects of fish oil supplementation on AD pathology: What’s next?. in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia. 2017;:33.
https://hdl.handle.net/21.15107/rcub_ibiss_6001 .

Lončarević-Vasiljković, Nataša, Jović, Milena, Ivković, Sanja, Milanović, Desanka, Dinić, Jelena, Brkić, Marjana, Avramović, Vladimir, Kanazir, Selma, "The newly discovered effects of fish oil supplementation on AD pathology: What’s next?" in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia (2017):33,
https://hdl.handle.net/21.15107/rcub_ibiss_6001 .

TY  - CONF
AU  - Jović, Milena
AU  - Lončarević-Vasiljković, Nataša
AU  - Avramović, Vladimir
AU  - Brkić, Marjana
AU  - Milanović, Desanka
AU  - Kanazir, Selma
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5804
AB  - Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative 
disease in elderly. Defining feature of AD pathology is the formation of amyloid 
plaques, structures that are composed of fibrillar Amyloid-β organized in a β-sheet 
conformation. In AD pathology the clinical symptoms mirror the pathological 
changes in the brain, where the neuronal loss and plaque pathology occur in the 
memory related areas. The onset of neuritic dystrophy represents the initial phase of 
neurodegeneration. It occurs in an early phase of pathology called latent phase, 
which leaves time frame for potential treatments. So far, omega 3 fatty acids 
(omega-3 FA), one of the main compounds of fish oil (FO), represent one of the most 
promising treatment. Here we investigated influence of omega-3 FA 
supplementation on number of plaques, Aβ load and neuritic dystrophy in parietal 
cortex in 5XFAD mice.
Methods: Three-month old female 5xFAD mice received FO (100 μl/animal/day) via 
oral gavage during a 3-week period. Number of plaques, total Aβ levels and neuritic 
dystrophy were visualized by immunohistochemistry and quantification was done by 
Image J software.
Results: Our results showed that 3 weeks of FO supplementation significantly 
decreased number of plaques, total Aβ levels and neuritic dystrophy in the parietal 
cortex of FO-supplemented 5xFAD animals as compared to non-supplemented 
5xFAD animals.
Conclusion: Since fish oil supplementation proved to be able to stop neuritic 
dystrophy in the parietal cortex of 5xFAD mice it may represent good approach for 
long term treatment in AD prevention.
PB  - Belgrade: University of Belgrade, Faculty of Biology
C3  - Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
T1  - Fish oil supplementation suppress neuritic dystrophy and Аβ pathology in parietal cortex of 5XFAD mice
SP  - 45
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5804
ER  - 

@conference{
author = "Jović, Milena and Lončarević-Vasiljković, Nataša and Avramović, Vladimir and Brkić, Marjana and Milanović, Desanka and Kanazir, Selma",
year = "2017",
abstract = "Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative 
disease in elderly. Defining feature of AD pathology is the formation of amyloid 
plaques, structures that are composed of fibrillar Amyloid-β organized in a β-sheet 
conformation. In AD pathology the clinical symptoms mirror the pathological 
changes in the brain, where the neuronal loss and plaque pathology occur in the 
memory related areas. The onset of neuritic dystrophy represents the initial phase of 
neurodegeneration. It occurs in an early phase of pathology called latent phase, 
which leaves time frame for potential treatments. So far, omega 3 fatty acids 
(omega-3 FA), one of the main compounds of fish oil (FO), represent one of the most 
promising treatment. Here we investigated influence of omega-3 FA 
supplementation on number of plaques, Aβ load and neuritic dystrophy in parietal 
cortex in 5XFAD mice.
Methods: Three-month old female 5xFAD mice received FO (100 μl/animal/day) via 
oral gavage during a 3-week period. Number of plaques, total Aβ levels and neuritic 
dystrophy were visualized by immunohistochemistry and quantification was done by 
Image J software.
Results: Our results showed that 3 weeks of FO supplementation significantly 
decreased number of plaques, total Aβ levels and neuritic dystrophy in the parietal 
cortex of FO-supplemented 5xFAD animals as compared to non-supplemented 
5xFAD animals.
Conclusion: Since fish oil supplementation proved to be able to stop neuritic 
dystrophy in the parietal cortex of 5xFAD mice it may represent good approach for 
long term treatment in AD prevention.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.",
title = "Fish oil supplementation suppress neuritic dystrophy and Аβ pathology in parietal cortex of 5XFAD mice",
pages = "45",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5804"
}

Jović, M., Lončarević-Vasiljković, N., Avramović, V., Brkić, M., Milanović, D.,& Kanazir, S.. (2017). Fish oil supplementation suppress neuritic dystrophy and Аβ pathology in parietal cortex of 5XFAD mice. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
Belgrade: University of Belgrade, Faculty of Biology., 45.
https://hdl.handle.net/21.15107/rcub_ibiss_5804

Jović M, Lončarević-Vasiljković N, Avramović V, Brkić M, Milanović D, Kanazir S. Fish oil supplementation suppress neuritic dystrophy and Аβ pathology in parietal cortex of 5XFAD mice. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.. 2017;:45.
https://hdl.handle.net/21.15107/rcub_ibiss_5804 .

Jović, Milena, Lončarević-Vasiljković, Nataša, Avramović, Vladimir, Brkić, Marjana, Milanović, Desanka, Kanazir, Selma, "Fish oil supplementation suppress neuritic dystrophy and Аβ pathology in parietal cortex of 5XFAD mice" in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia. (2017):45,
https://hdl.handle.net/21.15107/rcub_ibiss_5804 .

TY  - CONF
AU  - Lončarević-Vasiljković, Nataša
AU  - Jović, Milena
AU  - Ivković, Sanja
AU  - Milanović, Desanka
AU  - Brkić, Marjana
AU  - Avramović, Vladimir
AU  - Kanazir, Selma
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5715
AB  - Dystrophic neurites (DNs) are one of the neuropathological characteristics of Alzheimer's disease (AD) and represent the initial phase of neurodegeneration. Microtubule disruption in presynaptic dystrophic neurites that surround plaques impairs axonal transport and leads to the exacerbation of amyloid pathology in AD. Microglia plays a pivotal role in AD pathology as it is able to constitute a physical barrier around amyoid plaques and limit the accumulation of protofibrilar amylod beta around the fibrillar plaque core. In such a way microglia can mechanically shield the surrounding neurites from the neurotoxic protofibrillar Ai' aggregates. The use of supplements with omega-3 ( I%03) fatty acids (FAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), such as fish oil, is widespread due to proposed beneficial effects on the nervous system, High DHA consumption has been also associated with reduced risk and lessened AD pathology, yet the mechanisms and therapeutic potential of these supplements remain elusive. We analyzed the effects of the short-term fish oil (FO) supplementation on 4 months old 5xFAD mice, a mouse model with fast and robust development of the AD pathology hallmarks such as amyloid plaques and dystrophic neurites. We showed that even the short treatment with FO can affect the microglia clustering around amyloid plaques and increase the microglial plaque envelopment. Consequently, the Al2 accumulation was reduced and the appearance of DNs substantially suppressed. Our findings suggest that increased DHA consumption may play and important role in modulating microglial response and ameliorating AD pathology at least in the early phase of the disease.
PB  - Alzheimer's Association
C3  - AAIC Satellite Symposium: Aging and Alzheimer’s Disease: Opportunities for Therapeutic Interventions; 2017 Oct 19; Varna, Bulgaria
T1  - Short-term fish oil treatment suppresses the development of dystrophic neurites in the parietal cortex of 5XFAD AD mouse model during the early phase of the disease
SP  - 4B
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5715
ER  - 

@conference{
author = "Lončarević-Vasiljković, Nataša and Jović, Milena and Ivković, Sanja and Milanović, Desanka and Brkić, Marjana and Avramović, Vladimir and Kanazir, Selma",
year = "2017",
abstract = "Dystrophic neurites (DNs) are one of the neuropathological characteristics of Alzheimer's disease (AD) and represent the initial phase of neurodegeneration. Microtubule disruption in presynaptic dystrophic neurites that surround plaques impairs axonal transport and leads to the exacerbation of amyloid pathology in AD. Microglia plays a pivotal role in AD pathology as it is able to constitute a physical barrier around amyoid plaques and limit the accumulation of protofibrilar amylod beta around the fibrillar plaque core. In such a way microglia can mechanically shield the surrounding neurites from the neurotoxic protofibrillar Ai' aggregates. The use of supplements with omega-3 ( I%03) fatty acids (FAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), such as fish oil, is widespread due to proposed beneficial effects on the nervous system, High DHA consumption has been also associated with reduced risk and lessened AD pathology, yet the mechanisms and therapeutic potential of these supplements remain elusive. We analyzed the effects of the short-term fish oil (FO) supplementation on 4 months old 5xFAD mice, a mouse model with fast and robust development of the AD pathology hallmarks such as amyloid plaques and dystrophic neurites. We showed that even the short treatment with FO can affect the microglia clustering around amyloid plaques and increase the microglial plaque envelopment. Consequently, the Al2 accumulation was reduced and the appearance of DNs substantially suppressed. Our findings suggest that increased DHA consumption may play and important role in modulating microglial response and ameliorating AD pathology at least in the early phase of the disease.",
publisher = "Alzheimer's Association",
journal = "AAIC Satellite Symposium: Aging and Alzheimer’s Disease: Opportunities for Therapeutic Interventions; 2017 Oct 19; Varna, Bulgaria",
title = "Short-term fish oil treatment suppresses the development of dystrophic neurites in the parietal cortex of 5XFAD AD mouse model during the early phase of the disease",
pages = "4B",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5715"
}

Lončarević-Vasiljković, N., Jović, M., Ivković, S., Milanović, D., Brkić, M., Avramović, V.,& Kanazir, S.. (2017). Short-term fish oil treatment suppresses the development of dystrophic neurites in the parietal cortex of 5XFAD AD mouse model during the early phase of the disease. in AAIC Satellite Symposium: Aging and Alzheimer’s Disease: Opportunities for Therapeutic Interventions; 2017 Oct 19; Varna, Bulgaria
Alzheimer's Association., 4B.
https://hdl.handle.net/21.15107/rcub_ibiss_5715

Lončarević-Vasiljković N, Jović M, Ivković S, Milanović D, Brkić M, Avramović V, Kanazir S. Short-term fish oil treatment suppresses the development of dystrophic neurites in the parietal cortex of 5XFAD AD mouse model during the early phase of the disease. in AAIC Satellite Symposium: Aging and Alzheimer’s Disease: Opportunities for Therapeutic Interventions; 2017 Oct 19; Varna, Bulgaria. 2017;:4B.
https://hdl.handle.net/21.15107/rcub_ibiss_5715 .

Lončarević-Vasiljković, Nataša, Jović, Milena, Ivković, Sanja, Milanović, Desanka, Brkić, Marjana, Avramović, Vladimir, Kanazir, Selma, "Short-term fish oil treatment suppresses the development of dystrophic neurites in the parietal cortex of 5XFAD AD mouse model during the early phase of the disease" in AAIC Satellite Symposium: Aging and Alzheimer’s Disease: Opportunities for Therapeutic Interventions; 2017 Oct 19; Varna, Bulgaria (2017):4B,
https://hdl.handle.net/21.15107/rcub_ibiss_5715 .

TY  - CONF
AU  - Jović, Milena
AU  - Lončarević-Vasiljković, Nataša
AU  - Milanović, Desanka
AU  - Avramović, Vladimir
AU  - Brkić, Marjana
AU  - Kanazir, Selma
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5714
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and dementia. Pathologically, the disease is recognized by the presence of senile plaques (deposition of beta amyloid (Ap) peptides), neurofibrillary tangles, and neuronal loss. Clustering of microglial cells at sites of AO deposition in the brain is also an important pathological feature of AD. At present, there is no effective treatment for AD. 
To investigate the influence of fish oil (FO) supplementation, like potential treatment, we used transgenic 5xFAD mice which rapidly recapitulate major hallmarks of AD amyloid pathology. Three-month old female 5xFAD mice received FO (1001d/animallday) via oral gavage during 3 weeks period. Histological analysis was used to detect changes in pathological features of AD in parietal cortex in 5xFAD mice.ThioflavinS and AmiloGlo were used to visualize plaques, soluble Ap peptide was detect by A1342 antibody, SM131 antibody was used for neuritic dystrophy and lba-1 antibody for microglial cells. lmmunostaining was observed by confocal microscopy. Quantification was done by Image J program. 
We showed that short-term FO supplementation is capable of inducing significant decreased of number of plaques, total All levels, and preventing the emergence of neuritic dystrophy in parietal cortex of 5xFAD mice. Also, FO supplementation led to increase in overall microglial number, and enhanced clustering of microglial cells around amyloid plaques. We confirmed and extended previous findings suggesting that FO has a typical pleiotropic effect and we believe that FO in combination with others drugs could be good approach for long-term treatment in AD suppression.
PB  - Belgrade: Institute of Physics
C3  - Book of Abstracts: the Sixth International School and Conference on Photonics & COST actions: MP1406 and MP1402 & H2020-MSCA-RISE-2015 CARDIALLY workshop: PHOTONICA2017; 2017 Aug 28 - Sep 1; Belgrade, Serbia
T1  - The effect of short-term fish oil supplementation on Alzheimer disease-like pathology in 5xFAD mouse model
SP  - 126
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5714
ER  - 

@conference{
author = "Jović, Milena and Lončarević-Vasiljković, Nataša and Milanović, Desanka and Avramović, Vladimir and Brkić, Marjana and Kanazir, Selma",
year = "2017",
abstract = "Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and dementia. Pathologically, the disease is recognized by the presence of senile plaques (deposition of beta amyloid (Ap) peptides), neurofibrillary tangles, and neuronal loss. Clustering of microglial cells at sites of AO deposition in the brain is also an important pathological feature of AD. At present, there is no effective treatment for AD. 
To investigate the influence of fish oil (FO) supplementation, like potential treatment, we used transgenic 5xFAD mice which rapidly recapitulate major hallmarks of AD amyloid pathology. Three-month old female 5xFAD mice received FO (1001d/animallday) via oral gavage during 3 weeks period. Histological analysis was used to detect changes in pathological features of AD in parietal cortex in 5xFAD mice.ThioflavinS and AmiloGlo were used to visualize plaques, soluble Ap peptide was detect by A1342 antibody, SM131 antibody was used for neuritic dystrophy and lba-1 antibody for microglial cells. lmmunostaining was observed by confocal microscopy. Quantification was done by Image J program. 
We showed that short-term FO supplementation is capable of inducing significant decreased of number of plaques, total All levels, and preventing the emergence of neuritic dystrophy in parietal cortex of 5xFAD mice. Also, FO supplementation led to increase in overall microglial number, and enhanced clustering of microglial cells around amyloid plaques. We confirmed and extended previous findings suggesting that FO has a typical pleiotropic effect and we believe that FO in combination with others drugs could be good approach for long-term treatment in AD suppression.",
publisher = "Belgrade: Institute of Physics",
journal = "Book of Abstracts: the Sixth International School and Conference on Photonics & COST actions: MP1406 and MP1402 & H2020-MSCA-RISE-2015 CARDIALLY workshop: PHOTONICA2017; 2017 Aug 28 - Sep 1; Belgrade, Serbia",
title = "The effect of short-term fish oil supplementation on Alzheimer disease-like pathology in 5xFAD mouse model",
pages = "126",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5714"
}

Jović, M., Lončarević-Vasiljković, N., Milanović, D., Avramović, V., Brkić, M.,& Kanazir, S.. (2017). The effect of short-term fish oil supplementation on Alzheimer disease-like pathology in 5xFAD mouse model. in Book of Abstracts: the Sixth International School and Conference on Photonics & COST actions: MP1406 and MP1402 & H2020-MSCA-RISE-2015 CARDIALLY workshop: PHOTONICA2017; 2017 Aug 28 - Sep 1; Belgrade, Serbia
Belgrade: Institute of Physics., 126.
https://hdl.handle.net/21.15107/rcub_ibiss_5714

Jović M, Lončarević-Vasiljković N, Milanović D, Avramović V, Brkić M, Kanazir S. The effect of short-term fish oil supplementation on Alzheimer disease-like pathology in 5xFAD mouse model. in Book of Abstracts: the Sixth International School and Conference on Photonics & COST actions: MP1406 and MP1402 & H2020-MSCA-RISE-2015 CARDIALLY workshop: PHOTONICA2017; 2017 Aug 28 - Sep 1; Belgrade, Serbia. 2017;:126.
https://hdl.handle.net/21.15107/rcub_ibiss_5714 .

Jović, Milena, Lončarević-Vasiljković, Nataša, Milanović, Desanka, Avramović, Vladimir, Brkić, Marjana, Kanazir, Selma, "The effect of short-term fish oil supplementation on Alzheimer disease-like pathology in 5xFAD mouse model" in Book of Abstracts: the Sixth International School and Conference on Photonics & COST actions: MP1406 and MP1402 & H2020-MSCA-RISE-2015 CARDIALLY workshop: PHOTONICA2017; 2017 Aug 28 - Sep 1; Belgrade, Serbia (2017):126,
https://hdl.handle.net/21.15107/rcub_ibiss_5714 .

TY  - CONF
AU  - Avramović, Vladimir
AU  - Milanović, Desanka
AU  - Brkić, Marjana
AU  - Babić, Nikolina
AU  - Jović, Milena
AU  - Perović, Milka
AU  - Tešić, Vesna
AU  - Ivković, Sanja
AU  - Kanazir, Selma
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5829
AB  - Clinico-pathological features of Alzheimer's disease (AD) include memory loss, cognitive impairment, depression and social isolation. Epidemiological studies show a positive role of omega-3 poly-unsaturated fatty acids (n-3 PU FA) on prevention and mitigation of mild AD pathology. The 5xFAD mouse model used in this study bears five mutations linked to familiar forms of AD and recapitulates in a few months the main features of AD. This study was aimed to evaluate the effect of pre- and peri-natal omega-3 fatty acids supplementation on cognitive and non-cognitive behavior of 5xFAD mice . The fish oil, an abundant source of n-3 PUFA, was supplemented via oral gavages five days per week to dames throughout whole pregnancy and lactation. Six-month old offsprings were subjected to a battery of behavioral tests in order to assess typical rodent behavior, general locomotor activity, memory, depressive-like and social behavior. We have observed that the fish oil-supplemented 5xFAD offspring showed no changes in tests assessing typical rodent behavior, such as marble and nesting test, in comparison with 5XFAD control mice. When assessing depression and anxiety like behavior in a light-dark box, forced swim and open field behavioral tests significant changes were observed only between non-transgenic and transgenic mice. However, in three chambers test, used for assessing social behavior, fish oil- treated 5xFAD mice showed a significant increase in sociability, evaluated by increased time spent in compartment with, a mouse vs. empty compartment. Moreover, when the social novelty was tested through the introduction of a new mouse, the same trend was observed. This study shows that the pre- and peri-natal fish oil supplementation in 5xFAD mice can exert long-lasting effects inducing the significant improvement in some of the behavioral aspects of AD pathology in the adult offspring.
PB  - Belgrade: Serbian Nutrition Society
C3  - Book of Abstracts: 13th Congress of Nutrition Food and Nutrition: A Roadmap to Better Health; 2016 Oct 26-28; Belgrade, Serbia
T1  - Fish oil supplementation during pre- and peri-natal period: Behavioral phenotyping of transgenic mouse model of Alzheimer’s disease
SP  - 257
EP  - 258
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5829
ER  - 

@conference{
author = "Avramović, Vladimir and Milanović, Desanka and Brkić, Marjana and Babić, Nikolina and Jović, Milena and Perović, Milka and Tešić, Vesna and Ivković, Sanja and Kanazir, Selma",
year = "2016",
abstract = "Clinico-pathological features of Alzheimer's disease (AD) include memory loss, cognitive impairment, depression and social isolation. Epidemiological studies show a positive role of omega-3 poly-unsaturated fatty acids (n-3 PU FA) on prevention and mitigation of mild AD pathology. The 5xFAD mouse model used in this study bears five mutations linked to familiar forms of AD and recapitulates in a few months the main features of AD. This study was aimed to evaluate the effect of pre- and peri-natal omega-3 fatty acids supplementation on cognitive and non-cognitive behavior of 5xFAD mice . The fish oil, an abundant source of n-3 PUFA, was supplemented via oral gavages five days per week to dames throughout whole pregnancy and lactation. Six-month old offsprings were subjected to a battery of behavioral tests in order to assess typical rodent behavior, general locomotor activity, memory, depressive-like and social behavior. We have observed that the fish oil-supplemented 5xFAD offspring showed no changes in tests assessing typical rodent behavior, such as marble and nesting test, in comparison with 5XFAD control mice. When assessing depression and anxiety like behavior in a light-dark box, forced swim and open field behavioral tests significant changes were observed only between non-transgenic and transgenic mice. However, in three chambers test, used for assessing social behavior, fish oil- treated 5xFAD mice showed a significant increase in sociability, evaluated by increased time spent in compartment with, a mouse vs. empty compartment. Moreover, when the social novelty was tested through the introduction of a new mouse, the same trend was observed. This study shows that the pre- and peri-natal fish oil supplementation in 5xFAD mice can exert long-lasting effects inducing the significant improvement in some of the behavioral aspects of AD pathology in the adult offspring.",
publisher = "Belgrade: Serbian Nutrition Society",
journal = "Book of Abstracts: 13th Congress of Nutrition Food and Nutrition: A Roadmap to Better Health; 2016 Oct 26-28; Belgrade, Serbia",
title = "Fish oil supplementation during pre- and peri-natal period: Behavioral phenotyping of transgenic mouse model of Alzheimer’s disease",
pages = "257-258",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5829"
}

Avramović, V., Milanović, D., Brkić, M., Babić, N., Jović, M., Perović, M., Tešić, V., Ivković, S.,& Kanazir, S.. (2016). Fish oil supplementation during pre- and peri-natal period: Behavioral phenotyping of transgenic mouse model of Alzheimer’s disease. in Book of Abstracts: 13th Congress of Nutrition Food and Nutrition: A Roadmap to Better Health; 2016 Oct 26-28; Belgrade, Serbia
Belgrade: Serbian Nutrition Society., 257-258.
https://hdl.handle.net/21.15107/rcub_ibiss_5829

Avramović V, Milanović D, Brkić M, Babić N, Jović M, Perović M, Tešić V, Ivković S, Kanazir S. Fish oil supplementation during pre- and peri-natal period: Behavioral phenotyping of transgenic mouse model of Alzheimer’s disease. in Book of Abstracts: 13th Congress of Nutrition Food and Nutrition: A Roadmap to Better Health; 2016 Oct 26-28; Belgrade, Serbia. 2016;:257-258.
https://hdl.handle.net/21.15107/rcub_ibiss_5829 .

Avramović, Vladimir, Milanović, Desanka, Brkić, Marjana, Babić, Nikolina, Jović, Milena, Perović, Milka, Tešić, Vesna, Ivković, Sanja, Kanazir, Selma, "Fish oil supplementation during pre- and peri-natal period: Behavioral phenotyping of transgenic mouse model of Alzheimer’s disease" in Book of Abstracts: 13th Congress of Nutrition Food and Nutrition: A Roadmap to Better Health; 2016 Oct 26-28; Belgrade, Serbia (2016):257-258,
https://hdl.handle.net/21.15107/rcub_ibiss_5829 .

TY  - JOUR
AU  - Lončarević-Vasiljković, Nataša
AU  - Milanović, Desanka
AU  - Pešić, Vesna
AU  - Tešić, Vesna
AU  - Brkić, Marjana
AU  - Lazić, Divna
AU  - Avramović, Vladimir
AU  - Kanazir, Selma
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5437
AB  - Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. Using an animal model of TBI we examined the effect of dietary restriction (DR) on the neuroapoptosis and Bcl-2 family genes as the main regulators of the intrinsic apoptotic pathway. Bcl-2, Bcl-xl and Bax mRNA and protein expression in the ipsilateral cortex of adult Wistar rats exposed to DR before TBI were studied from 2 to 28 days post injury. Our results showed that DR suppressed neuroapoptosis and promoted significant upregulation of antiapoptotic Bcl-2 and Bcl-xl mRNAs in the ipsilateral cortex following injury. Expression of the proapoptotic Bax gene increased in ad libitum (AL) fed rats but remained unchanged in rats exposed to DR. Although the expression of Bcl-2, Bcl-xl and Bax proteins was changed in a similar manner in both experimental groups, DR promoted a continuous increase in the Bcl-2:Bax protein ratio throughout the recovery period. Together with our previous finding that DR mediates inhibition of the extrinsic apoptotic pathway the present work reveals that modulation of the intrinsic pathway contributes to the beneficial effect of DR in brain injury. These findings provide new insight into the effects of DR on pro-survival signaling after injury, lending further support to its neuroprotective effect.
PB  - England : Elsevier
T2  - Neurochemistry International
T1  - Dietary restriction suppresses apoptotic cell death, promotes Bcl-2 and Bcl-xl mRNA expression and increases the Bcl-2/Bax protein ratio in the rat cortex after cortical injury.
VL  - 96
DO  - 10.1016/j.neuint.2016.02.017
SP  - 69
EP  - 76
ER  - 

@article{
author = "Lončarević-Vasiljković, Nataša and Milanović, Desanka and Pešić, Vesna and Tešić, Vesna and Brkić, Marjana and Lazić, Divna and Avramović, Vladimir and Kanazir, Selma",
year = "2016",
abstract = "Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. Using an animal model of TBI we examined the effect of dietary restriction (DR) on the neuroapoptosis and Bcl-2 family genes as the main regulators of the intrinsic apoptotic pathway. Bcl-2, Bcl-xl and Bax mRNA and protein expression in the ipsilateral cortex of adult Wistar rats exposed to DR before TBI were studied from 2 to 28 days post injury. Our results showed that DR suppressed neuroapoptosis and promoted significant upregulation of antiapoptotic Bcl-2 and Bcl-xl mRNAs in the ipsilateral cortex following injury. Expression of the proapoptotic Bax gene increased in ad libitum (AL) fed rats but remained unchanged in rats exposed to DR. Although the expression of Bcl-2, Bcl-xl and Bax proteins was changed in a similar manner in both experimental groups, DR promoted a continuous increase in the Bcl-2:Bax protein ratio throughout the recovery period. Together with our previous finding that DR mediates inhibition of the extrinsic apoptotic pathway the present work reveals that modulation of the intrinsic pathway contributes to the beneficial effect of DR in brain injury. These findings provide new insight into the effects of DR on pro-survival signaling after injury, lending further support to its neuroprotective effect.",
publisher = "England : Elsevier",
journal = "Neurochemistry International",
title = "Dietary restriction suppresses apoptotic cell death, promotes Bcl-2 and Bcl-xl mRNA expression and increases the Bcl-2/Bax protein ratio in the rat cortex after cortical injury.",
volume = "96",
doi = "10.1016/j.neuint.2016.02.017",
pages = "69-76"
}

Lončarević-Vasiljković, N., Milanović, D., Pešić, V., Tešić, V., Brkić, M., Lazić, D., Avramović, V.,& Kanazir, S.. (2016). Dietary restriction suppresses apoptotic cell death, promotes Bcl-2 and Bcl-xl mRNA expression and increases the Bcl-2/Bax protein ratio in the rat cortex after cortical injury.. in Neurochemistry International
England : Elsevier., 96, 69-76.
https://doi.org/10.1016/j.neuint.2016.02.017

Lončarević-Vasiljković N, Milanović D, Pešić V, Tešić V, Brkić M, Lazić D, Avramović V, Kanazir S. Dietary restriction suppresses apoptotic cell death, promotes Bcl-2 and Bcl-xl mRNA expression and increases the Bcl-2/Bax protein ratio in the rat cortex after cortical injury.. in Neurochemistry International. 2016;96:69-76.
doi:10.1016/j.neuint.2016.02.017 .

Lončarević-Vasiljković, Nataša, Milanović, Desanka, Pešić, Vesna, Tešić, Vesna, Brkić, Marjana, Lazić, Divna, Avramović, Vladimir, Kanazir, Selma, "Dietary restriction suppresses apoptotic cell death, promotes Bcl-2 and Bcl-xl mRNA expression and increases the Bcl-2/Bax protein ratio in the rat cortex after cortical injury." in Neurochemistry International, 96 (2016):69-76,
https://doi.org/10.1016/j.neuint.2016.02.017 . .