TY  - JOUR
AU  - Jeremić, Rada
AU  - Peković, Sanja
AU  - Lavrnja, Irena
AU  - Bjelobaba, Ivana
AU  - Đelić, Marina
AU  - Dacić, Sanja
AU  - Brkić, Predrag D
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5975
AB  - A growing body of evidence suggests that hyperbaric oxygenation (HBO) may affect the activity of adult neural stem cells (NSCs). Since the role of NSCs in recovery from brain injury is still unclear, the purpose of this study was to investigate the effects of sensorimotor cortex ablation (SCA) and HBO treatment (HBOT) on the processes of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus that is the site of adult neurogenesis. Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), Sham control (S, animals that underwent the surgical procedure without opening the skull), SCA (animals in whom the right sensorimotor cortex was removed via suction ablation), and SCA + HBO (operated animals that passed HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. Using immunohistochemistry and double immunofluorescence labeling, we show that SCA causes significant loss of neurons in the DG. Newborn neurons in the subgranular zone (SGZ), inner-third, and partially mid-third of the granule cell layer are predominantly affected by SCA. HBOT decreases the SCA-caused loss of immature neurons, prevents reduction of dendritic arborization, and increases proliferation of progenitor cells. Our results suggest a protective effect of HBO by reducing the vulnerability of immature neurons in the adult DG to SCA injury.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury
IS  - 5
VL  - 24
DO  - 10.3390/ijms24054261
SP  - 4261
ER  - 

@article{
author = "Jeremić, Rada and Peković, Sanja and Lavrnja, Irena and Bjelobaba, Ivana and Đelić, Marina and Dacić, Sanja and Brkić, Predrag D",
year = "2023",
abstract = "A growing body of evidence suggests that hyperbaric oxygenation (HBO) may affect the activity of adult neural stem cells (NSCs). Since the role of NSCs in recovery from brain injury is still unclear, the purpose of this study was to investigate the effects of sensorimotor cortex ablation (SCA) and HBO treatment (HBOT) on the processes of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus that is the site of adult neurogenesis. Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), Sham control (S, animals that underwent the surgical procedure without opening the skull), SCA (animals in whom the right sensorimotor cortex was removed via suction ablation), and SCA + HBO (operated animals that passed HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. Using immunohistochemistry and double immunofluorescence labeling, we show that SCA causes significant loss of neurons in the DG. Newborn neurons in the subgranular zone (SGZ), inner-third, and partially mid-third of the granule cell layer are predominantly affected by SCA. HBOT decreases the SCA-caused loss of immature neurons, prevents reduction of dendritic arborization, and increases proliferation of progenitor cells. Our results suggest a protective effect of HBO by reducing the vulnerability of immature neurons in the adult DG to SCA injury.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury",
number = "5",
volume = "24",
doi = "10.3390/ijms24054261",
pages = "4261"
}

Jeremić, R., Peković, S., Lavrnja, I., Bjelobaba, I., Đelić, M., Dacić, S.,& Brkić, P. D.. (2023). Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury. in International Journal of Molecular Sciences
Basel: MDPI., 24(5), 4261.
https://doi.org/10.3390/ijms24054261

Jeremić R, Peković S, Lavrnja I, Bjelobaba I, Đelić M, Dacić S, Brkić PD. Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury. in International Journal of Molecular Sciences. 2023;24(5):4261.
doi:10.3390/ijms24054261 .

Jeremić, Rada, Peković, Sanja, Lavrnja, Irena, Bjelobaba, Ivana, Đelić, Marina, Dacić, Sanja, Brkić, Predrag D, "Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury" in International Journal of Molecular Sciences, 24, no. 5 (2023):4261,
https://doi.org/10.3390/ijms24054261 . .

TY  - CONF
AU  - Jeremić, Rada
AU  - Peković, Sanja
AU  - Lavrnja, Irena
AU  - Bjelobaba, Ivana
AU  - Đelić, Marina N
AU  - Brkić, Predrag D
AU  - Dacić, Sanja
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5984
AB  - Introduction: There is growing evidence that hyperbaric oxygenation (HBO) can affect adult neural stem cells (NSCs) activity. Because the role of NSCs in recovery from brain injury is still unclear, this study examined how ablation of the sensorimotor cortex (SCA) and HBO treatment (HBOT) affect the process of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus considered to be the site of adult neurogenesis. Material and methods: Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), SCA (animals in which the right sensorimotor cortex was removed by suction ablation), and SCA+HBO (operated animals subjected to HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. The effects of HBOT were monitored by immunohistochemistry and double immunofluorescence labeling. In addition, the number of DCX+ cells was determined along the length of the SGZ in the inner and separately in the outer blade of the right dentate gyrus. Also, the total dendrite length was measured and the number of branching points, dendrite terminals, and segments were counted to quantify dendritic arborization in each neuron. Results: HBOT decreases SCA-induced loss of immature neurons, prevents reduction of dendritic branching, and increases proliferation of progenitor cells. Conclusion: Our results suggest a protective effect of HBOT by reducing the vulnerability of immature neurons in the adult DG to SCA injury.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury
SP  - 78
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5984
ER  - 

@conference{
author = "Jeremić, Rada and Peković, Sanja and Lavrnja, Irena and Bjelobaba, Ivana and Đelić, Marina N and Brkić, Predrag D and Dacić, Sanja",
year = "2023",
abstract = "Introduction: There is growing evidence that hyperbaric oxygenation (HBO) can affect adult neural stem cells (NSCs) activity. Because the role of NSCs in recovery from brain injury is still unclear, this study examined how ablation of the sensorimotor cortex (SCA) and HBO treatment (HBOT) affect the process of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus considered to be the site of adult neurogenesis. Material and methods: Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), SCA (animals in which the right sensorimotor cortex was removed by suction ablation), and SCA+HBO (operated animals subjected to HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. The effects of HBOT were monitored by immunohistochemistry and double immunofluorescence labeling. In addition, the number of DCX+ cells was determined along the length of the SGZ in the inner and separately in the outer blade of the right dentate gyrus. Also, the total dendrite length was measured and the number of branching points, dendrite terminals, and segments were counted to quantify dendritic arborization in each neuron. Results: HBOT decreases SCA-induced loss of immature neurons, prevents reduction of dendritic branching, and increases proliferation of progenitor cells. Conclusion: Our results suggest a protective effect of HBOT by reducing the vulnerability of immature neurons in the adult DG to SCA injury.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury",
pages = "78",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5984"
}

Jeremić, R., Peković, S., Lavrnja, I., Bjelobaba, I., Đelić, M. N., Brkić, P. D.,& Dacić, S.. (2023). Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 78.
https://hdl.handle.net/21.15107/rcub_ibiss_5984

Jeremić R, Peković S, Lavrnja I, Bjelobaba I, Đelić MN, Brkić PD, Dacić S. Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:78.
https://hdl.handle.net/21.15107/rcub_ibiss_5984 .

Jeremić, Rada, Peković, Sanja, Lavrnja, Irena, Bjelobaba, Ivana, Đelić, Marina N, Brkić, Predrag D, Dacić, Sanja, "Hyperbaric oxygen prevents dendrite degeneration and loss of DCX-positive newborn immature neurons in the dentate gyrus after traumatic brain injury" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):78,
https://hdl.handle.net/21.15107/rcub_ibiss_5984 .

TY  - JOUR
AU  - Mandić, Marija
AU  - Mitić, Katarina
AU  - Nedeljković, Predrag
AU  - Perić, Mina
AU  - Božić, Bojan
AU  - Lunić, Tanja
AU  - Bačić, Ana
AU  - Rajilić-Stojanović, Mirjana
AU  - Peković, Sanja
AU  - Božić Nedeljković, Biljana
PY  - 2022
UR  - https://www.mdpi.com/2072-6643/14/6/1273
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35334928
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8955508
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4940
AB  - The present study aimed to investigate the neuroprotective effects of the vitamin B complex (B1, B2, B3, B5, B6, and B12-VBC), by studying the changes in the femoral nerve, quadriceps muscle, popliteal lymph nodes and gut microbiota in the rat model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). VBC treatment attenuated clinical signs of EAE during the disease, and reduced the duration of EAE thereby contributing to a faster recovery. In VBC-treated EAE rats, a significant decrease in nerve and muscle nuclear density was revealed during the onset period of the disease, while a marked increase was detected at the end of the disease, compared with untreated EAE rats. In the lymph nodes of VBC-treated EAE rats, a fewer number of lymphoid follicles in the cortical area and smaller epithelioid granulomas were detected. The changes in microbiota composition were examined using 16S rRNA gene sequencing and bioinformatics analysis, which revealed the potential of VBC treatment in establishing and/or maintaining gut microbiota homeostasis. Finally, the present study demonstrated that VBC treatment ameliorated the cellular changes in the affected peripheral nerve, muscles innervated by this nerve, and the gut microbiota dysbiosis which occurred during the EAE.
PB  - Basel: MDPI
T2  - Nutrients
T1  - Vitamin B Complex and Experimental Autoimmune Encephalomyelitis -Attenuation of the Clinical Signs and Gut Microbiota Dysbiosis.
IS  - 6
VL  - 14
DO  - 10.3390/nu14061273
SP  - 1273
ER  - 

@article{
author = "Mandić, Marija and Mitić, Katarina and Nedeljković, Predrag and Perić, Mina and Božić, Bojan and Lunić, Tanja and Bačić, Ana and Rajilić-Stojanović, Mirjana and Peković, Sanja and Božić Nedeljković, Biljana",
year = "2022",
abstract = "The present study aimed to investigate the neuroprotective effects of the vitamin B complex (B1, B2, B3, B5, B6, and B12-VBC), by studying the changes in the femoral nerve, quadriceps muscle, popliteal lymph nodes and gut microbiota in the rat model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). VBC treatment attenuated clinical signs of EAE during the disease, and reduced the duration of EAE thereby contributing to a faster recovery. In VBC-treated EAE rats, a significant decrease in nerve and muscle nuclear density was revealed during the onset period of the disease, while a marked increase was detected at the end of the disease, compared with untreated EAE rats. In the lymph nodes of VBC-treated EAE rats, a fewer number of lymphoid follicles in the cortical area and smaller epithelioid granulomas were detected. The changes in microbiota composition were examined using 16S rRNA gene sequencing and bioinformatics analysis, which revealed the potential of VBC treatment in establishing and/or maintaining gut microbiota homeostasis. Finally, the present study demonstrated that VBC treatment ameliorated the cellular changes in the affected peripheral nerve, muscles innervated by this nerve, and the gut microbiota dysbiosis which occurred during the EAE.",
publisher = "Basel: MDPI",
journal = "Nutrients",
title = "Vitamin B Complex and Experimental Autoimmune Encephalomyelitis -Attenuation of the Clinical Signs and Gut Microbiota Dysbiosis.",
number = "6",
volume = "14",
doi = "10.3390/nu14061273",
pages = "1273"
}

Mandić, M., Mitić, K., Nedeljković, P., Perić, M., Božić, B., Lunić, T., Bačić, A., Rajilić-Stojanović, M., Peković, S.,& Božić Nedeljković, B.. (2022). Vitamin B Complex and Experimental Autoimmune Encephalomyelitis -Attenuation of the Clinical Signs and Gut Microbiota Dysbiosis.. in Nutrients
Basel: MDPI., 14(6), 1273.
https://doi.org/10.3390/nu14061273

Mandić M, Mitić K, Nedeljković P, Perić M, Božić B, Lunić T, Bačić A, Rajilić-Stojanović M, Peković S, Božić Nedeljković B. Vitamin B Complex and Experimental Autoimmune Encephalomyelitis -Attenuation of the Clinical Signs and Gut Microbiota Dysbiosis.. in Nutrients. 2022;14(6):1273.
doi:10.3390/nu14061273 .

Mandić, Marija, Mitić, Katarina, Nedeljković, Predrag, Perić, Mina, Božić, Bojan, Lunić, Tanja, Bačić, Ana, Rajilić-Stojanović, Mirjana, Peković, Sanja, Božić Nedeljković, Biljana, "Vitamin B Complex and Experimental Autoimmune Encephalomyelitis -Attenuation of the Clinical Signs and Gut Microbiota Dysbiosis." in Nutrients, 14, no. 6 (2022):1273,
https://doi.org/10.3390/nu14061273 . .

TY  - CONF
AU  - Pislar, A.
AU  - Tratnjek, L.
AU  - Božić, B.
AU  - Glavan, G.
AU  - Zidar, N.
AU  - Peković, Sanja
AU  - Zivin, M.
AU  - Kos, J.
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4451
AB  - Inflammation is closely implicated in the pathogenesis of several
neurodegenerative disorders, including Parkinson’s disease (PD) and multiple sclerosis (MS), where the hallmark of neuroinflammation
is activated microglia. Microglia-derived lysosomal
cathepsins have been increasingly recognized as important inflammatory
mediators that trigger signalling pathways that aggravate
neuroinflammation. In the past, a contribution to neuroinflammation
processes has been shown for cathepsin X in vitro, however;
the expression patterns and functional roles of cathepsin X
in neuroinflammatory brain pathology remained elusive. Our
recent studies revealed a strong neuroinflammation-induced
upregulation of cathepsin X expression and activity using in vivo
models that mimic the pathology of PD and MS, respectively.
Unilateral injection of lipopolysaccharide into the rat striatum
induced strong upregulation of cathepsin X expression and its
activity in the ipsilateral striatum and in other brain areas such
as cerebral cortex, corpus callosum, subventricular zone and
external globus pallidus, whereas the upregulation was mainly
restricted to activated microglia and reactive astrocytes. Similarly,
a marked increase in expression and activity of cathepsin X
was observed in spinal cord in rat model of experimental autoimmune
encephalomyelitis. Additionally, cathepsin X upregulation
was observed in injured peripheral nerve, localized in the inflammatory
cell type, M1 macrophages. Nevertheless, continuous
administration of the cathepsin X inhibitor showed moderate
protective effects against neuroinflammation-induced degeneration;
further indicating that cathepsin X plays a role as a pathogenic
factor in neuroinflammation-induced neurodegeneration
and represents a potential therapeutic target for neurodegenerative
diseases associated with inflammation.
PB  - Hoboken: Wiley
C3  - FEBS OpenBio
T1  - Inhibition of cathepsin X as a novel strategy for the treatment of neuroinflammation-associated diseases
IS  - Supplement 1
VL  - 11
DO  - 10.1002/2211-5463.13206
SP  - 59
EP  - 60
ER  - 

@conference{
author = "Pislar, A. and Tratnjek, L. and Božić, B. and Glavan, G. and Zidar, N. and Peković, Sanja and Zivin, M. and Kos, J.",
year = "2021",
abstract = "Inflammation is closely implicated in the pathogenesis of several
neurodegenerative disorders, including Parkinson’s disease (PD) and multiple sclerosis (MS), where the hallmark of neuroinflammation
is activated microglia. Microglia-derived lysosomal
cathepsins have been increasingly recognized as important inflammatory
mediators that trigger signalling pathways that aggravate
neuroinflammation. In the past, a contribution to neuroinflammation
processes has been shown for cathepsin X in vitro, however;
the expression patterns and functional roles of cathepsin X
in neuroinflammatory brain pathology remained elusive. Our
recent studies revealed a strong neuroinflammation-induced
upregulation of cathepsin X expression and activity using in vivo
models that mimic the pathology of PD and MS, respectively.
Unilateral injection of lipopolysaccharide into the rat striatum
induced strong upregulation of cathepsin X expression and its
activity in the ipsilateral striatum and in other brain areas such
as cerebral cortex, corpus callosum, subventricular zone and
external globus pallidus, whereas the upregulation was mainly
restricted to activated microglia and reactive astrocytes. Similarly,
a marked increase in expression and activity of cathepsin X
was observed in spinal cord in rat model of experimental autoimmune
encephalomyelitis. Additionally, cathepsin X upregulation
was observed in injured peripheral nerve, localized in the inflammatory
cell type, M1 macrophages. Nevertheless, continuous
administration of the cathepsin X inhibitor showed moderate
protective effects against neuroinflammation-induced degeneration;
further indicating that cathepsin X plays a role as a pathogenic
factor in neuroinflammation-induced neurodegeneration
and represents a potential therapeutic target for neurodegenerative
diseases associated with inflammation.",
publisher = "Hoboken: Wiley",
journal = "FEBS OpenBio",
title = "Inhibition of cathepsin X as a novel strategy for the treatment of neuroinflammation-associated diseases",
number = "Supplement 1",
volume = "11",
doi = "10.1002/2211-5463.13206",
pages = "59-60"
}

Pislar, A., Tratnjek, L., Božić, B., Glavan, G., Zidar, N., Peković, S., Zivin, M.,& Kos, J.. (2021). Inhibition of cathepsin X as a novel strategy for the treatment of neuroinflammation-associated diseases. in FEBS OpenBio
Hoboken: Wiley., 11(Supplement 1), 59-60.
https://doi.org/10.1002/2211-5463.13206

Pislar A, Tratnjek L, Božić B, Glavan G, Zidar N, Peković S, Zivin M, Kos J. Inhibition of cathepsin X as a novel strategy for the treatment of neuroinflammation-associated diseases. in FEBS OpenBio. 2021;11(Supplement 1):59-60.
doi:10.1002/2211-5463.13206 .

Pislar, A., Tratnjek, L., Božić, B., Glavan, G., Zidar, N., Peković, Sanja, Zivin, M., Kos, J., "Inhibition of cathepsin X as a novel strategy for the treatment of neuroinflammation-associated diseases" in FEBS OpenBio, 11, no. Supplement 1 (2021):59-60,
https://doi.org/10.1002/2211-5463.13206 . .

TY  - JOUR
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Božić, Iva
AU  - Milošević, Katarina
AU  - Jakovljević, Marija
AU  - Peković, Sanja
AU  - Stojilkovic, Stanko S.
AU  - Bjelobaba, Ivana
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32592862
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6149
AB  - Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.
PB  - Elsevier BV
PB  - Elsevier
T2  - Brain, Behavior, and Immunity
T1  - The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.
VL  - 89
DO  - 10.1016/j.bbi.2020.06.025
SP  - 233
EP  - 244
ER  - 

@article{
author = "Milošević, Ana and Janjić, Marija and Lavrnja, Irena and Savić, Danijela and Božić, Iva and Milošević, Katarina and Jakovljević, Marija and Peković, Sanja and Stojilkovic, Stanko S. and Bjelobaba, Ivana",
year = "2020",
abstract = "Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.",
publisher = "Elsevier BV, Elsevier",
journal = "Brain, Behavior, and Immunity",
title = "The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.",
volume = "89",
doi = "10.1016/j.bbi.2020.06.025",
pages = "233-244"
}

Milošević, A., Janjić, M., Lavrnja, I., Savić, D., Božić, I., Milošević, K., Jakovljević, M., Peković, S., Stojilkovic, S. S.,& Bjelobaba, I.. (2020). The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.. in Brain, Behavior, and Immunity
Elsevier BV., 89, 233-244.
https://doi.org/10.1016/j.bbi.2020.06.025

Milošević A, Janjić M, Lavrnja I, Savić D, Božić I, Milošević K, Jakovljević M, Peković S, Stojilkovic SS, Bjelobaba I. The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.. in Brain, Behavior, and Immunity. 2020;89:233-244.
doi:10.1016/j.bbi.2020.06.025 .

Milošević, Ana, Janjić, Marija, Lavrnja, Irena, Savić, Danijela, Božić, Iva, Milošević, Katarina, Jakovljević, Marija, Peković, Sanja, Stojilkovic, Stanko S., Bjelobaba, Ivana, "The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis." in Brain, Behavior, and Immunity, 89 (2020):233-244,
https://doi.org/10.1016/j.bbi.2020.06.025 . .

TY  - JOUR
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Božić, Iva
AU  - Milošević, Katarina
AU  - Jakovljević, Marija
AU  - Peković, Sanja
AU  - Stojilkovic, Stanko S.
AU  - Bjelobaba, Ivana
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32592862
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3762
AB  - Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.
PB  - Elsevier BV
T2  - Brain, Behavior, and Immunity
T1  - The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.
VL  - 89
DO  - 10.1016/j.bbi.2020.06.025
SP  - DOI:10.1016/j.bbi.2020.06.025
EP  - 244
ER  - 

@article{
author = "Milošević, Ana and Janjić, Marija and Lavrnja, Irena and Savić, Danijela and Božić, Iva and Milošević, Katarina and Jakovljević, Marija and Peković, Sanja and Stojilkovic, Stanko S. and Bjelobaba, Ivana",
year = "2020",
abstract = "Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.",
publisher = "Elsevier BV",
journal = "Brain, Behavior, and Immunity",
title = "The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.",
volume = "89",
doi = "10.1016/j.bbi.2020.06.025",
pages = "DOI:10.1016/j.bbi.2020.06.025-244"
}

Milošević, A., Janjić, M., Lavrnja, I., Savić, D., Božić, I., Milošević, K., Jakovljević, M., Peković, S., Stojilkovic, S. S.,& Bjelobaba, I.. (2020). The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.. in Brain, Behavior, and Immunity
Elsevier BV., 89, DOI:10.1016/j.bbi.2020.06.025-244.
https://doi.org/10.1016/j.bbi.2020.06.025

Milošević A, Janjić M, Lavrnja I, Savić D, Božić I, Milošević K, Jakovljević M, Peković S, Stojilkovic SS, Bjelobaba I. The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.. in Brain, Behavior, and Immunity. 2020;89:DOI:10.1016/j.bbi.2020.06.025-244.
doi:10.1016/j.bbi.2020.06.025 .

Milošević, Ana, Janjić, Marija, Lavrnja, Irena, Savić, Danijela, Božić, Iva, Milošević, Katarina, Jakovljević, Marija, Peković, Sanja, Stojilkovic, Stanko S., Bjelobaba, Ivana, "The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis." in Brain, Behavior, and Immunity, 89 (2020):DOI:10.1016/j.bbi.2020.06.025-244,
https://doi.org/10.1016/j.bbi.2020.06.025 . .

TY  - JOUR
AU  - Ćupić Miladinović, Dejana
AU  - Prevendar Crnić, Andreja
AU  - Peković, Sanja
AU  - Dacić, Sanja
AU  - Ivanović, Saša
AU  - Santibanez, Juan Francisco
AU  - Ćupić, Vitomir
AU  - Borozan, Nevena
AU  - Antonijević Miljaković, Evica
AU  - Borozan, Sunčica
PY  - 2020
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0009279720315908
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33166511
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4007
AB  - Chlorpyrifos is a extensively used organophosphate pesticide (OP). In this study, we closely looked into neurotoxicity of CPF and effect of vitamin B1, by checking the levels of cholinesterases, determining the activity of parameters of oxidative stress, inflammation and also level of apoptotic regulator. The study was performed on a total of 80 male Japanese quails (Coturnix japonica), (two control and 6 experimental groups, n = 10). Three group of quails were given by gavage chlorpyrifos (CPF) for 7 consecutive days at doses of 1.50 mg/kg b.w., 3.00 mg/kg b.w., and 6.00 mg/kg b.w. Another three groups were treated with 10 mg/kg b.w. of vitamin B1 i.m. 30 min after CPF application (in above mentioned doses). Our study have proved that all doses of CPF significantly inhibited cholinesterases in brain, while vitamin B1 reactivated them. CPF has led to an increase in the concentration of malondialdehyde (MDA), and activity of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), while tiamin changed the activity of antioxidant enzymes: CAT, SOD, GST. CPF stimulated apoptosis by decreasing B-cell lymphoma (Bcl-2) in brain, while application of vitamin B1 caused an increase of this parameter. CPF amplified inflammatory effect by elevating levels of inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2). Thiamine proved its anti-inflammatory property by decreasing the expression of iNOS and interleukin-1(IL-1) and interleukin-6(IL-6). This study is highly pertinent because there is little defense currently available to humans and animals to prevent toxic effects of pesticides.
PB  - Elsevier BV
T2  - Chemico-Biological Interactions
T1  - Recovery of brain cholinesterases and effect on parameters of oxidative stres and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration.
DO  - 10.1016/j.cbi.2020.109312
SP  - 109312
ER  - 

@article{
author = "Ćupić Miladinović, Dejana and Prevendar Crnić, Andreja and Peković, Sanja and Dacić, Sanja and Ivanović, Saša and Santibanez, Juan Francisco and Ćupić, Vitomir and Borozan, Nevena and Antonijević Miljaković, Evica and Borozan, Sunčica",
year = "2020",
abstract = "Chlorpyrifos is a extensively used organophosphate pesticide (OP). In this study, we closely looked into neurotoxicity of CPF and effect of vitamin B1, by checking the levels of cholinesterases, determining the activity of parameters of oxidative stress, inflammation and also level of apoptotic regulator. The study was performed on a total of 80 male Japanese quails (Coturnix japonica), (two control and 6 experimental groups, n = 10). Three group of quails were given by gavage chlorpyrifos (CPF) for 7 consecutive days at doses of 1.50 mg/kg b.w., 3.00 mg/kg b.w., and 6.00 mg/kg b.w. Another three groups were treated with 10 mg/kg b.w. of vitamin B1 i.m. 30 min after CPF application (in above mentioned doses). Our study have proved that all doses of CPF significantly inhibited cholinesterases in brain, while vitamin B1 reactivated them. CPF has led to an increase in the concentration of malondialdehyde (MDA), and activity of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), while tiamin changed the activity of antioxidant enzymes: CAT, SOD, GST. CPF stimulated apoptosis by decreasing B-cell lymphoma (Bcl-2) in brain, while application of vitamin B1 caused an increase of this parameter. CPF amplified inflammatory effect by elevating levels of inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2). Thiamine proved its anti-inflammatory property by decreasing the expression of iNOS and interleukin-1(IL-1) and interleukin-6(IL-6). This study is highly pertinent because there is little defense currently available to humans and animals to prevent toxic effects of pesticides.",
publisher = "Elsevier BV",
journal = "Chemico-Biological Interactions",
title = "Recovery of brain cholinesterases and effect on parameters of oxidative stres and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration.",
doi = "10.1016/j.cbi.2020.109312",
pages = "109312"
}

Ćupić Miladinović, D., Prevendar Crnić, A., Peković, S., Dacić, S., Ivanović, S., Santibanez, J. F., Ćupić, V., Borozan, N., Antonijević Miljaković, E.,& Borozan, S.. (2020). Recovery of brain cholinesterases and effect on parameters of oxidative stres and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration.. in Chemico-Biological Interactions
Elsevier BV., 109312.
https://doi.org/10.1016/j.cbi.2020.109312

Ćupić Miladinović D, Prevendar Crnić A, Peković S, Dacić S, Ivanović S, Santibanez JF, Ćupić V, Borozan N, Antonijević Miljaković E, Borozan S. Recovery of brain cholinesterases and effect on parameters of oxidative stres and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration.. in Chemico-Biological Interactions. 2020;:109312.
doi:10.1016/j.cbi.2020.109312 .

Ćupić Miladinović, Dejana, Prevendar Crnić, Andreja, Peković, Sanja, Dacić, Sanja, Ivanović, Saša, Santibanez, Juan Francisco, Ćupić, Vitomir, Borozan, Nevena, Antonijević Miljaković, Evica, Borozan, Sunčica, "Recovery of brain cholinesterases and effect on parameters of oxidative stres and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration." in Chemico-Biological Interactions (2020):109312,
https://doi.org/10.1016/j.cbi.2020.109312 . .

TY  - JOUR
AU  - Ehmedah, Adil
AU  - Nedeljković, Predrag
AU  - Dacić, Sanja
AU  - Repac, Jelena
AU  - Drašković-Pavlović, Biljana
AU  - Vučević, Dragana
AU  - Peković, Sanja
AU  - Božić Nedeljković, Biljana
PY  - 2020
UR  - https://www.mdpi.com/1420-3049/25/22/5426
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4034
AB  - Peripheral nerve injury (PNI) triggers a complex multi-cellular response involving the injured neurons, Schwann cells (SCs), and immune cells, often resulting in poor functional recovery. The aim of this study was to investigate the effects of the treatment with vitamin B (B1, B2, B3, B5, B6, and B12) complex on the interaction between macrophages and SCs during the recovery period after PNI. Transection of the motor branch of the femoral nerve followed by reconstruction by termino-terminal anastomosis was used as an experimental model. Isolated nerves from the sham (S), operated (O), and operated groups treated with the B vitamins (OT group) were used for immunofluorescence analysis. The obtained data indicated that PNI modulates interactions between macrophages and SCs in a time-dependent manner. The treatment with B vitamins complex promoted the M1-to M2-macrophage polarization and accelerated the transition from the non-myelin to myelin-forming SCs, an indicative of SCs maturation. The effect of B vitamins complex on both cell types was accompanied with an increase in macrophage/SC interactions, all of which correlated with the regeneration of the injured nerve. Clearly, the capacity of B vitamins to modulate macrophages-SCs interaction may be promising for the treatment of PNI.
PB  - NLM (Medline)
T2  - Molecules
T1  - Effect of Vitamin B Complex Treatment on Macrophages to Schwann Cells Association during Neuroinflammation after Peripheral Nerve Injury
IS  - 22
VL  - 25
DO  - 10.3390/molecules25225426
SP  - 5426
ER  - 

@article{
author = "Ehmedah, Adil and Nedeljković, Predrag and Dacić, Sanja and Repac, Jelena and Drašković-Pavlović, Biljana and Vučević, Dragana and Peković, Sanja and Božić Nedeljković, Biljana",
year = "2020",
abstract = "Peripheral nerve injury (PNI) triggers a complex multi-cellular response involving the injured neurons, Schwann cells (SCs), and immune cells, often resulting in poor functional recovery. The aim of this study was to investigate the effects of the treatment with vitamin B (B1, B2, B3, B5, B6, and B12) complex on the interaction between macrophages and SCs during the recovery period after PNI. Transection of the motor branch of the femoral nerve followed by reconstruction by termino-terminal anastomosis was used as an experimental model. Isolated nerves from the sham (S), operated (O), and operated groups treated with the B vitamins (OT group) were used for immunofluorescence analysis. The obtained data indicated that PNI modulates interactions between macrophages and SCs in a time-dependent manner. The treatment with B vitamins complex promoted the M1-to M2-macrophage polarization and accelerated the transition from the non-myelin to myelin-forming SCs, an indicative of SCs maturation. The effect of B vitamins complex on both cell types was accompanied with an increase in macrophage/SC interactions, all of which correlated with the regeneration of the injured nerve. Clearly, the capacity of B vitamins to modulate macrophages-SCs interaction may be promising for the treatment of PNI.",
publisher = "NLM (Medline)",
journal = "Molecules",
title = "Effect of Vitamin B Complex Treatment on Macrophages to Schwann Cells Association during Neuroinflammation after Peripheral Nerve Injury",
number = "22",
volume = "25",
doi = "10.3390/molecules25225426",
pages = "5426"
}

Ehmedah, A., Nedeljković, P., Dacić, S., Repac, J., Drašković-Pavlović, B., Vučević, D., Peković, S.,& Božić Nedeljković, B.. (2020). Effect of Vitamin B Complex Treatment on Macrophages to Schwann Cells Association during Neuroinflammation after Peripheral Nerve Injury. in Molecules
NLM (Medline)., 25(22), 5426.
https://doi.org/10.3390/molecules25225426

Ehmedah A, Nedeljković P, Dacić S, Repac J, Drašković-Pavlović B, Vučević D, Peković S, Božić Nedeljković B. Effect of Vitamin B Complex Treatment on Macrophages to Schwann Cells Association during Neuroinflammation after Peripheral Nerve Injury. in Molecules. 2020;25(22):5426.
doi:10.3390/molecules25225426 .

Ehmedah, Adil, Nedeljković, Predrag, Dacić, Sanja, Repac, Jelena, Drašković-Pavlović, Biljana, Vučević, Dragana, Peković, Sanja, Božić Nedeljković, Biljana, "Effect of Vitamin B Complex Treatment on Macrophages to Schwann Cells Association during Neuroinflammation after Peripheral Nerve Injury" in Molecules, 25, no. 22 (2020):5426,
https://doi.org/10.3390/molecules25225426 . .

TY  - JOUR
AU  - Pantić, Igor
AU  - Jeremić, Rada
AU  - Dacić, Sanja
AU  - Peković, Sanja
AU  - Pantić, Senka
AU  - Đelić, Marina
AU  - Vitić, Zagorka
AU  - Brkić, Predrag
AU  - Brodski, Claude
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3599
AB  - Traumatic brain injury (TBI) is a main cause of death and disabilities in young adults. Although learning and memory impairments are a major clinical manifestation of TBI, the consequences of TBI on the hippocampus are still not well understood. In particular, how lesions to the sensorimotor cortex damage the hippocampus, to which it is not directly connected, is still elusive. Here, we study the effects of sensorimotor cortex ablation (SCA) on the hippocampal dentate gyrus, by applying a highly sensitive gray-level co-occurrence matrix (GLCM) analysis. Using GLCM analysis of granule neurons, we discovered, in our TBI paradigm, subtle changes in granule cell (GC) morphology, including textual uniformity, contrast, and variance, which is not detected by conventional microscopy. We conclude that sensorimotor cortex trauma leads to specific changes in the hippocampus that advance our understanding of the cellular underpinnings of cognitive impairments in TBI. Moreover, we identified GLCM analysis as a highly sensitive method to detect subtle changes in the GC layers that is expected to significantly improve further studies investigating the impact of TBI on hippocampal neuropathology.
T2  - Microscopy and Microanalysis
T1  - Gray-Level Co-Occurrence Matrix Analysis of Granule Neurons of the Hippocampal Dentate Gyrus Following Cortical Injury.
IS  - 1
VL  - 26
DO  - 10.1017/S143192762000001X
SP  - 166
EP  - 172
ER  - 

@article{
author = "Pantić, Igor and Jeremić, Rada and Dacić, Sanja and Peković, Sanja and Pantić, Senka and Đelić, Marina and Vitić, Zagorka and Brkić, Predrag and Brodski, Claude",
year = "2020",
abstract = "Traumatic brain injury (TBI) is a main cause of death and disabilities in young adults. Although learning and memory impairments are a major clinical manifestation of TBI, the consequences of TBI on the hippocampus are still not well understood. In particular, how lesions to the sensorimotor cortex damage the hippocampus, to which it is not directly connected, is still elusive. Here, we study the effects of sensorimotor cortex ablation (SCA) on the hippocampal dentate gyrus, by applying a highly sensitive gray-level co-occurrence matrix (GLCM) analysis. Using GLCM analysis of granule neurons, we discovered, in our TBI paradigm, subtle changes in granule cell (GC) morphology, including textual uniformity, contrast, and variance, which is not detected by conventional microscopy. We conclude that sensorimotor cortex trauma leads to specific changes in the hippocampus that advance our understanding of the cellular underpinnings of cognitive impairments in TBI. Moreover, we identified GLCM analysis as a highly sensitive method to detect subtle changes in the GC layers that is expected to significantly improve further studies investigating the impact of TBI on hippocampal neuropathology.",
journal = "Microscopy and Microanalysis",
title = "Gray-Level Co-Occurrence Matrix Analysis of Granule Neurons of the Hippocampal Dentate Gyrus Following Cortical Injury.",
number = "1",
volume = "26",
doi = "10.1017/S143192762000001X",
pages = "166-172"
}

Pantić, I., Jeremić, R., Dacić, S., Peković, S., Pantić, S., Đelić, M., Vitić, Z., Brkić, P.,& Brodski, C.. (2020). Gray-Level Co-Occurrence Matrix Analysis of Granule Neurons of the Hippocampal Dentate Gyrus Following Cortical Injury.. in Microscopy and Microanalysis, 26(1), 166-172.
https://doi.org/10.1017/S143192762000001X

Pantić I, Jeremić R, Dacić S, Peković S, Pantić S, Đelić M, Vitić Z, Brkić P, Brodski C. Gray-Level Co-Occurrence Matrix Analysis of Granule Neurons of the Hippocampal Dentate Gyrus Following Cortical Injury.. in Microscopy and Microanalysis. 2020;26(1):166-172.
doi:10.1017/S143192762000001X .

Pantić, Igor, Jeremić, Rada, Dacić, Sanja, Peković, Sanja, Pantić, Senka, Đelić, Marina, Vitić, Zagorka, Brkić, Predrag, Brodski, Claude, "Gray-Level Co-Occurrence Matrix Analysis of Granule Neurons of the Hippocampal Dentate Gyrus Following Cortical Injury." in Microscopy and Microanalysis, 26, no. 1 (2020):166-172,
https://doi.org/10.1017/S143192762000001X . .

TY  - CONF
AU  - Božić, Iva
AU  - Milošević, Katarina
AU  - Janjić, Marija
AU  - Savić, Danijela
AU  - Laketa, Danijela
AU  - Jakovljević, Marija
AU  - Milošević, Ana
AU  - Peković, Sanja
AU  - Lavrnja, Irena
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6006
AB  - Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination, neurodegeneration and gliosis. It is considered as a perplexing multifactorial disease in which the neuroendocrine system plays an important role. Growth hormone (GH) is synthesized and secreted by the somatotroph cells of the anterior pituitary. GH secretion is positively regulated by the hypothalamic factor GHRH and exerts its effects through interaction with the GH receptor (GHR), a member of the class I cytokine receptor family. It was demonstrated that neurons and astrocytes also produce GH and that GHR is widely expressed in the CNS. Nonetheless, it is not known whether expression pattern of GHR changes in the CNS during MS. We investigated GHR expression in the spinal cord during the course of experimental autoimmune encephalomyelitis (EAE), animal model of MS that is broadly used. Our results show that GHR is diminished on mRNA and protein level during EAE. Double immunofluorescence studies demonstrated that GHR is expressed in different cell types in the spinal cord in physiological conditions, including astrocytes and microglia. This expression pattern does not change extensively after the onset of EAE. However, at the peak of disease GHR is absent from astrocytes in the white and grey matter, but still present in microglia, although to a lesser degree. At the end of disease, when the animals have recovered, GHR expression is similar to control conditions. Our results point to complex involvement of GHR in the pathology of EAE.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Expression of growth hormone receptor (GHR) in experimental autoimmune encephalomyelitis
EP  - 212
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6006
ER  - 

@conference{
author = "Božić, Iva and Milošević, Katarina and Janjić, Marija and Savić, Danijela and Laketa, Danijela and Jakovljević, Marija and Milošević, Ana and Peković, Sanja and Lavrnja, Irena",
year = "2019",
abstract = "Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination, neurodegeneration and gliosis. It is considered as a perplexing multifactorial disease in which the neuroendocrine system plays an important role. Growth hormone (GH) is synthesized and secreted by the somatotroph cells of the anterior pituitary. GH secretion is positively regulated by the hypothalamic factor GHRH and exerts its effects through interaction with the GH receptor (GHR), a member of the class I cytokine receptor family. It was demonstrated that neurons and astrocytes also produce GH and that GHR is widely expressed in the CNS. Nonetheless, it is not known whether expression pattern of GHR changes in the CNS during MS. We investigated GHR expression in the spinal cord during the course of experimental autoimmune encephalomyelitis (EAE), animal model of MS that is broadly used. Our results show that GHR is diminished on mRNA and protein level during EAE. Double immunofluorescence studies demonstrated that GHR is expressed in different cell types in the spinal cord in physiological conditions, including astrocytes and microglia. This expression pattern does not change extensively after the onset of EAE. However, at the peak of disease GHR is absent from astrocytes in the white and grey matter, but still present in microglia, although to a lesser degree. At the end of disease, when the animals have recovered, GHR expression is similar to control conditions. Our results point to complex involvement of GHR in the pathology of EAE.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Expression of growth hormone receptor (GHR) in experimental autoimmune encephalomyelitis",
pages = "212",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6006"
}

Božić, I., Milošević, K., Janjić, M., Savić, D., Laketa, D., Jakovljević, M., Milošević, A., Peković, S.,& Lavrnja, I.. (2019). Expression of growth hormone receptor (GHR) in experimental autoimmune encephalomyelitis. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society..
https://hdl.handle.net/21.15107/rcub_ibiss_6006

Božić I, Milošević K, Janjić M, Savić D, Laketa D, Jakovljević M, Milošević A, Peković S, Lavrnja I. Expression of growth hormone receptor (GHR) in experimental autoimmune encephalomyelitis. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:null-212.
https://hdl.handle.net/21.15107/rcub_ibiss_6006 .

Božić, Iva, Milošević, Katarina, Janjić, Marija, Savić, Danijela, Laketa, Danijela, Jakovljević, Marija, Milošević, Ana, Peković, Sanja, Lavrnja, Irena, "Expression of growth hormone receptor (GHR) in experimental autoimmune encephalomyelitis" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019),
https://hdl.handle.net/21.15107/rcub_ibiss_6006 .

TY  - CONF
AU  - Milošević, Katarina
AU  - Lavrnja, Irena
AU  - Janjić, Marija
AU  - Božić, Iva
AU  - Laketa, Danijela
AU  - Dacić, Sanja
AU  - Peković, Sanja
AU  - Savić, Danijela
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6004
AB  - Traumatic brain injury triggers neuroinflammatory response mediated by distinct populations of myeloid cells, including central nervous system (CNS) resident macrophages - microglia. Depending on the time upon insult this response may either contribute to restorative effects or hinder CNS repair.
Therefore, the focus of this study was on determining temporal course in gene expression profiles of markers specific to the mononuclear phagocyte system (MPS).
We have used the model of cortical stab injury which was performed on 3-months-old male Wistar rats. All animals were divided into 3 experimental groups: control, sham and lesion group and sacrificed at 1, 2, 3 and 7 days post-injury. After brain isolation, mRNA was extracted from cortical pieces around the center of lesion (the same tissue part was used for sham and control groups). The gene expression was analyzed by real-time PCR.
The mRNA levels of Itgam, Aif-1, Cd68 and Cx3Cr1, which are surface markers of MPS, were increased in first two days after brain injury, and then all, except Cd68, showed declining trend compared to control group. Furthermore, we analyzed expression of Arg-1, Il-6 and Tnf-alpha genes, which could be indicators of pro- or anti-inflammatory milieu. All of them increased significantly in the first two days post-injury, and then returned to control level, with the most prominent changes detected in Arg-1 mRNA level.
This study indicates enhanced MPS response in the acute phase after cortical stab injury. Further studies are required to determine which populations of CNS myeloid cells predominate in specific time point upon injury.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Mononuclear Phagocyte System In Traumatic Brain Injury
SP  - 503
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6004
ER  - 

@conference{
author = "Milošević, Katarina and Lavrnja, Irena and Janjić, Marija and Božić, Iva and Laketa, Danijela and Dacić, Sanja and Peković, Sanja and Savić, Danijela",
year = "2019",
abstract = "Traumatic brain injury triggers neuroinflammatory response mediated by distinct populations of myeloid cells, including central nervous system (CNS) resident macrophages - microglia. Depending on the time upon insult this response may either contribute to restorative effects or hinder CNS repair.
Therefore, the focus of this study was on determining temporal course in gene expression profiles of markers specific to the mononuclear phagocyte system (MPS).
We have used the model of cortical stab injury which was performed on 3-months-old male Wistar rats. All animals were divided into 3 experimental groups: control, sham and lesion group and sacrificed at 1, 2, 3 and 7 days post-injury. After brain isolation, mRNA was extracted from cortical pieces around the center of lesion (the same tissue part was used for sham and control groups). The gene expression was analyzed by real-time PCR.
The mRNA levels of Itgam, Aif-1, Cd68 and Cx3Cr1, which are surface markers of MPS, were increased in first two days after brain injury, and then all, except Cd68, showed declining trend compared to control group. Furthermore, we analyzed expression of Arg-1, Il-6 and Tnf-alpha genes, which could be indicators of pro- or anti-inflammatory milieu. All of them increased significantly in the first two days post-injury, and then returned to control level, with the most prominent changes detected in Arg-1 mRNA level.
This study indicates enhanced MPS response in the acute phase after cortical stab injury. Further studies are required to determine which populations of CNS myeloid cells predominate in specific time point upon injury.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Mononuclear Phagocyte System In Traumatic Brain Injury",
pages = "503",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6004"
}

Milošević, K., Lavrnja, I., Janjić, M., Božić, I., Laketa, D., Dacić, S., Peković, S.,& Savić, D.. (2019). Mononuclear Phagocyte System In Traumatic Brain Injury. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society., 503.
https://hdl.handle.net/21.15107/rcub_ibiss_6004

Milošević K, Lavrnja I, Janjić M, Božić I, Laketa D, Dacić S, Peković S, Savić D. Mononuclear Phagocyte System In Traumatic Brain Injury. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:503.
https://hdl.handle.net/21.15107/rcub_ibiss_6004 .

Milošević, Katarina, Lavrnja, Irena, Janjić, Marija, Božić, Iva, Laketa, Danijela, Dacić, Sanja, Peković, Sanja, Savić, Danijela, "Mononuclear Phagocyte System In Traumatic Brain Injury" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):503,
https://hdl.handle.net/21.15107/rcub_ibiss_6004 .

TY  - JOUR
AU  - Božić, Iva
AU  - Savić, Danijela
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Laketa, Danijela
AU  - Milošević, Katarina
AU  - Bjelobaba, Ivana
AU  - Jakovljević, Marija
AU  - Nedeljković, Nadežda
AU  - Peković, Sanja
AU  - Lavrnja, Irena
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5874
AB  - Multiple sclerosis (MS) is a chronic, inflammatory, neurodegenerative disease with an autoimmune component. It was suggested that potassium channels, which are involved in crucial biological functions may have a role in different diseases, including MS and its animal model, experimental autoimmune encephalomyelitis (EAE). It was shown that voltage-gated potassium channels Kv1.5 are responsible for fine-tuning in the immune physiology and influence proliferation and differentiation in microglia and astrocytes. Here, we explored the cellular distribution of the Kv1.5 channel, together with its transcript and protein expression in the male rat spinal cord during different stages of EAE. Our results reveal a decrease of Kv1.5 transcript and protein level at the peak of disease, where massive infiltration of myeloid cells occurs, together with reactive astrogliosis and demyelination. Also, we revealed that the presence of this channel is not found in infiltrating macrophages/microglia during EAE. It is interesting to note that Kv1.5 channel is expressed only in resting microglia in the naïve animals. Predominant expression of Kv1.5 channel was found in the astrocytes in all experimental groups, while some vimentin+ cells, resembling macrophages, are devoid of Kv1.5 expression. Our results point to the possible link between Kv1.5 channel and the pathophysiological processes in EAE.
PB  - New York: Springer
T2  - Neurochemical Research
T1  - The Potassium Channel Kv1.5 Expression Alters During Experimental  Autoimmune Encephalomyelitis
IS  - 12
VL  - 44
DO  - 10.1007/s11064-019-02892-4
SP  - 2733
EP  - 2745
ER  - 

@article{
author = "Božić, Iva and Savić, Danijela and Milošević, Ana and Janjić, Marija and Laketa, Danijela and Milošević, Katarina and Bjelobaba, Ivana and Jakovljević, Marija and Nedeljković, Nadežda and Peković, Sanja and Lavrnja, Irena",
year = "2019",
abstract = "Multiple sclerosis (MS) is a chronic, inflammatory, neurodegenerative disease with an autoimmune component. It was suggested that potassium channels, which are involved in crucial biological functions may have a role in different diseases, including MS and its animal model, experimental autoimmune encephalomyelitis (EAE). It was shown that voltage-gated potassium channels Kv1.5 are responsible for fine-tuning in the immune physiology and influence proliferation and differentiation in microglia and astrocytes. Here, we explored the cellular distribution of the Kv1.5 channel, together with its transcript and protein expression in the male rat spinal cord during different stages of EAE. Our results reveal a decrease of Kv1.5 transcript and protein level at the peak of disease, where massive infiltration of myeloid cells occurs, together with reactive astrogliosis and demyelination. Also, we revealed that the presence of this channel is not found in infiltrating macrophages/microglia during EAE. It is interesting to note that Kv1.5 channel is expressed only in resting microglia in the naïve animals. Predominant expression of Kv1.5 channel was found in the astrocytes in all experimental groups, while some vimentin+ cells, resembling macrophages, are devoid of Kv1.5 expression. Our results point to the possible link between Kv1.5 channel and the pathophysiological processes in EAE.",
publisher = "New York: Springer",
journal = "Neurochemical Research",
title = "The Potassium Channel Kv1.5 Expression Alters During Experimental  Autoimmune Encephalomyelitis",
number = "12",
volume = "44",
doi = "10.1007/s11064-019-02892-4",
pages = "2733-2745"
}

Božić, I., Savić, D., Milošević, A., Janjić, M., Laketa, D., Milošević, K., Bjelobaba, I., Jakovljević, M., Nedeljković, N., Peković, S.,& Lavrnja, I.. (2019). The Potassium Channel Kv1.5 Expression Alters During Experimental  Autoimmune Encephalomyelitis. in Neurochemical Research
New York: Springer., 44(12), 2733-2745.
https://doi.org/10.1007/s11064-019-02892-4

Božić I, Savić D, Milošević A, Janjić M, Laketa D, Milošević K, Bjelobaba I, Jakovljević M, Nedeljković N, Peković S, Lavrnja I. The Potassium Channel Kv1.5 Expression Alters During Experimental  Autoimmune Encephalomyelitis. in Neurochemical Research. 2019;44(12):2733-2745.
doi:10.1007/s11064-019-02892-4 .

Božić, Iva, Savić, Danijela, Milošević, Ana, Janjić, Marija, Laketa, Danijela, Milošević, Katarina, Bjelobaba, Ivana, Jakovljević, Marija, Nedeljković, Nadežda, Peković, Sanja, Lavrnja, Irena, "The Potassium Channel Kv1.5 Expression Alters During Experimental  Autoimmune Encephalomyelitis" in Neurochemical Research, 44, no. 12 (2019):2733-2745,
https://doi.org/10.1007/s11064-019-02892-4 . .

TY  - CONF
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Lavrnja, Irena
AU  - Peković, Sanja
AU  - Bjelobaba, Ivana
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5979
AB  - Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease, two to three times more common in women than in men. Because the effects of neuroinflammation on the reproductive status have not been fully explored, our aim was to investigate the impact of experimental autoimmune encephalomyelitis (EAE), the rat model of MS, on hypothalamo-pituitary-gonadal axis. EAE was actively induced in Dark-Agouti rats of both sexes. The animals were examined daily for disease symptoms, weight changes, and estrous cycle phase. The animals were sacrificed at the onset, peak, and end of the disease. Hypothalamic and pituitary tissues were dissected for qRT-PCR analyses. Blood was collected for LH measurements. In separate experiments, groups of male and female animals at the peak of EAE and naïve controls received a subcutaneous injection of buserelin acetate, a potent synthetic GnRH analogue. The obtained data implied that hypothalamic neuroinflammation occurs during onset and/or peak of the disease in both sexes (upregulation of Gfap, Il1b, Il6, Ccl2 and Spp1 mRNA expression). However, hypothalamic Kiss1 and Gnrh mRNA expression was affected differently in males and females, as well as mRNA expression of pituitary signature genes - Lhb, Fshb and Gnrhr. LH levels drop transiently following the course of the disease; in females, this drop coincided with the arrest in diestrus. Nevertheless, the pituitary remained responsive to buserelin treatment. Our results indicate that EAE affects the regulation of hypothalamo-pituitary-gonadal axis in both sexes. Further analyses are needed to elucidate the causes and details of differences in hypothalamic response to neuroinflammation.
PB  - Belgrade: Faculty of Pharmacy
C3  - Abstract Book: 2nd Symposium in Biomedicine: Basic and Clinical Neuroscience; 2019 May 9; Belgrade, Serbia
T1  - Sex differences in the regulatory changes of HPG axis during experimental autoimmune encephalomyelitis in rats
SP  - 11
EP  - 12
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5979
ER  - 

@conference{
author = "Milošević, Ana and Janjić, Marija and Lavrnja, Irena and Peković, Sanja and Bjelobaba, Ivana",
year = "2019",
abstract = "Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease, two to three times more common in women than in men. Because the effects of neuroinflammation on the reproductive status have not been fully explored, our aim was to investigate the impact of experimental autoimmune encephalomyelitis (EAE), the rat model of MS, on hypothalamo-pituitary-gonadal axis. EAE was actively induced in Dark-Agouti rats of both sexes. The animals were examined daily for disease symptoms, weight changes, and estrous cycle phase. The animals were sacrificed at the onset, peak, and end of the disease. Hypothalamic and pituitary tissues were dissected for qRT-PCR analyses. Blood was collected for LH measurements. In separate experiments, groups of male and female animals at the peak of EAE and naïve controls received a subcutaneous injection of buserelin acetate, a potent synthetic GnRH analogue. The obtained data implied that hypothalamic neuroinflammation occurs during onset and/or peak of the disease in both sexes (upregulation of Gfap, Il1b, Il6, Ccl2 and Spp1 mRNA expression). However, hypothalamic Kiss1 and Gnrh mRNA expression was affected differently in males and females, as well as mRNA expression of pituitary signature genes - Lhb, Fshb and Gnrhr. LH levels drop transiently following the course of the disease; in females, this drop coincided with the arrest in diestrus. Nevertheless, the pituitary remained responsive to buserelin treatment. Our results indicate that EAE affects the regulation of hypothalamo-pituitary-gonadal axis in both sexes. Further analyses are needed to elucidate the causes and details of differences in hypothalamic response to neuroinflammation.",
publisher = "Belgrade: Faculty of Pharmacy",
journal = "Abstract Book: 2nd Symposium in Biomedicine: Basic and Clinical Neuroscience; 2019 May 9; Belgrade, Serbia",
title = "Sex differences in the regulatory changes of HPG axis during experimental autoimmune encephalomyelitis in rats",
pages = "11-12",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5979"
}

Milošević, A., Janjić, M., Lavrnja, I., Peković, S.,& Bjelobaba, I.. (2019). Sex differences in the regulatory changes of HPG axis during experimental autoimmune encephalomyelitis in rats. in Abstract Book: 2nd Symposium in Biomedicine: Basic and Clinical Neuroscience; 2019 May 9; Belgrade, Serbia
Belgrade: Faculty of Pharmacy., 11-12.
https://hdl.handle.net/21.15107/rcub_ibiss_5979

Milošević A, Janjić M, Lavrnja I, Peković S, Bjelobaba I. Sex differences in the regulatory changes of HPG axis during experimental autoimmune encephalomyelitis in rats. in Abstract Book: 2nd Symposium in Biomedicine: Basic and Clinical Neuroscience; 2019 May 9; Belgrade, Serbia. 2019;:11-12.
https://hdl.handle.net/21.15107/rcub_ibiss_5979 .

Milošević, Ana, Janjić, Marija, Lavrnja, Irena, Peković, Sanja, Bjelobaba, Ivana, "Sex differences in the regulatory changes of HPG axis during experimental autoimmune encephalomyelitis in rats" in Abstract Book: 2nd Symposium in Biomedicine: Basic and Clinical Neuroscience; 2019 May 9; Belgrade, Serbia (2019):11-12,
https://hdl.handle.net/21.15107/rcub_ibiss_5979 .

TY  - CONF
AU  - Jakovljević, Marija
AU  - Lavrnja, Irena
AU  - Božić, Iva
AU  - Milošević, Ana
AU  - Bjelobaba, Ivana
AU  - Savić, Danijela
AU  - Peković, Sanja
AU  - Nedeljković, Nadežda
AU  - Laketa, Danijela
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5982
AB  - Considering neuroinflammatory paradigm, increased extracellular levels of ATP have adverse effects, while adenosine is predominantly anti-inflammatory. In the CNS, NTPDase1/CD39 is the main enzyme that initiates the degradation pathway of extracellular ATP to adenosine. The aim of the study was to explore the activation state of the cells that express NTPDase1/CD39 – microglia and macrophages, during experimental autoimmune encephalomyelitis (EAE). Acute monophasic EAE was induced in female Dark Agouti rats. Animals were sacrificed at the disease onset (Eo), peak (Ep) and end (Ee). The lumbosacral parts of spinal cords were isolated for gene (qRT-PCR and in situ hybridization) and protein expression analysis (Western Blot, immunofluorescence and flow cytometry). Activation state of microglia/macrophages was assessed by colocalization analysis of NTPDase1/Iba1 and NTPDase1/CD68 with iNOS or Arg1 as specific markers of pro- and antiinflammatory state, respectively. During EAE, NTPDase1/CD39 was significantly increased both at mRNA and protein level at Ep. Immunofluorescence combined with flow cytometry showed that reactive microglia and mononuclear infiltrates accounted for the most of the observed increase. Both Iba1 and CD68 microglia/macrophage markers showed higher co-occurrence with iNOS at Eo and Arg1 at Ep, suggesting prevalence of M1-like at Eo and M2-like at Ep. In addition, NTPDase1 showed about three-times higher colocalization with Arg1 compared to iNOS at Ep, suggesting its higher association with M2-like activation state of microglia/ macrophages. Together, our data suggest an association between NTPDase1 up-regulation by reactive microglia and infiltrated macrophages and their transition toward anti-inflammatory phenotype in EAE.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - NTPDase1/CD39 Expression Increased During EAE in Association with Number and Activation State of Microglia/Macrophages
SP  - 492
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5982
ER  - 

@conference{
author = "Jakovljević, Marija and Lavrnja, Irena and Božić, Iva and Milošević, Ana and Bjelobaba, Ivana and Savić, Danijela and Peković, Sanja and Nedeljković, Nadežda and Laketa, Danijela",
year = "2019",
abstract = "Considering neuroinflammatory paradigm, increased extracellular levels of ATP have adverse effects, while adenosine is predominantly anti-inflammatory. In the CNS, NTPDase1/CD39 is the main enzyme that initiates the degradation pathway of extracellular ATP to adenosine. The aim of the study was to explore the activation state of the cells that express NTPDase1/CD39 – microglia and macrophages, during experimental autoimmune encephalomyelitis (EAE). Acute monophasic EAE was induced in female Dark Agouti rats. Animals were sacrificed at the disease onset (Eo), peak (Ep) and end (Ee). The lumbosacral parts of spinal cords were isolated for gene (qRT-PCR and in situ hybridization) and protein expression analysis (Western Blot, immunofluorescence and flow cytometry). Activation state of microglia/macrophages was assessed by colocalization analysis of NTPDase1/Iba1 and NTPDase1/CD68 with iNOS or Arg1 as specific markers of pro- and antiinflammatory state, respectively. During EAE, NTPDase1/CD39 was significantly increased both at mRNA and protein level at Ep. Immunofluorescence combined with flow cytometry showed that reactive microglia and mononuclear infiltrates accounted for the most of the observed increase. Both Iba1 and CD68 microglia/macrophage markers showed higher co-occurrence with iNOS at Eo and Arg1 at Ep, suggesting prevalence of M1-like at Eo and M2-like at Ep. In addition, NTPDase1 showed about three-times higher colocalization with Arg1 compared to iNOS at Ep, suggesting its higher association with M2-like activation state of microglia/ macrophages. Together, our data suggest an association between NTPDase1 up-regulation by reactive microglia and infiltrated macrophages and their transition toward anti-inflammatory phenotype in EAE.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "NTPDase1/CD39 Expression Increased During EAE in Association with Number and Activation State of Microglia/Macrophages",
pages = "492",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5982"
}

Jakovljević, M., Lavrnja, I., Božić, I., Milošević, A., Bjelobaba, I., Savić, D., Peković, S., Nedeljković, N.,& Laketa, D.. (2019). NTPDase1/CD39 Expression Increased During EAE in Association with Number and Activation State of Microglia/Macrophages. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 492.
https://hdl.handle.net/21.15107/rcub_ibiss_5982

Jakovljević M, Lavrnja I, Božić I, Milošević A, Bjelobaba I, Savić D, Peković S, Nedeljković N, Laketa D. NTPDase1/CD39 Expression Increased During EAE in Association with Number and Activation State of Microglia/Macrophages. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:492.
https://hdl.handle.net/21.15107/rcub_ibiss_5982 .

Jakovljević, Marija, Lavrnja, Irena, Božić, Iva, Milošević, Ana, Bjelobaba, Ivana, Savić, Danijela, Peković, Sanja, Nedeljković, Nadežda, Laketa, Danijela, "NTPDase1/CD39 Expression Increased During EAE in Association with Number and Activation State of Microglia/Macrophages" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):492,
https://hdl.handle.net/21.15107/rcub_ibiss_5982 .

TY  - JOUR
AU  - Dacić, Sanja
AU  - Božić, Iva
AU  - Jeremić, Rada
AU  - Bjelobaba, Ivana
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Rakić, Ljubisav
AU  - Stojiljković, Mirjana
AU  - Peković, Sanja
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5989
AB  - Aims: Traumatic brain injury (TBI) causes disruption in homeostasis of calcium ions (Ca2+), important second messenger considered as the major culprit of secondary injury and TBI-induced neuronal damage and death. Ca2+ entry into the cells occurs via various types of voltage-dependent calcium channels (VDCCs). The aim of this study was to evaluate the involvement of Ca2+ entry via L-type CaV1.2 VDCCs in the processes of neuroinflammation and regeneration after brain injury. Methods: TBI was performed on male Wistar rats by sensorimotor cortex ablation (SCA) at the following coordinates: 2 mm anterior and 4 mm posterior to bregma, and 4 mm lateral from the midline. Temporal and cellular pattern of CaV1.2 expression was followed at different time points post-injury (2, 7, 14, 30 dpi) using double immunofluorescence staining with specific markers. Results: Upregulation of CaV1.2 expression was detected on reactive astrocytes and astrocytic processes that form glial scar around the lesion site, on subset of proinflammatory microglia/macrophages and neutrophils surrounding the lesion cavity. Interestingly, presence of CaV1.2+ cells was detected in the migratory pathway, consisted of DCX+ progenitors, extending from subventricular zone up to the lesion site. Furthermore, CaV1.2+/DCX+ newborn neurons were detected in subgranular layer of hippocampal dentate gyrus. Conclusions: We concluded that L-type CaV1.2 calcium channel has an important role in the regulation of processes of neuroinflammation, neuroregeneration and neurogenesis, pointing to the complexity of intercellular regulation of Ca2+ homeostasis after brain injury. Consequently, modulation of CaV1.2 channels expression may be potential target for the treatment of brain injury.
PB  - Belgrade: Serbian Neuroscience Society
T2  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - L-type Calcium Channels Involvement in the Regulation of Neuroinflammation and Neuroregeneration After Brain Injury
SP  - 487
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5989
ER  - 

@article{
author = "Dacić, Sanja and Božić, Iva and Jeremić, Rada and Bjelobaba, Ivana and Lavrnja, Irena and Savić, Danijela and Rakić, Ljubisav and Stojiljković, Mirjana and Peković, Sanja",
year = "2019",
abstract = "Aims: Traumatic brain injury (TBI) causes disruption in homeostasis of calcium ions (Ca2+), important second messenger considered as the major culprit of secondary injury and TBI-induced neuronal damage and death. Ca2+ entry into the cells occurs via various types of voltage-dependent calcium channels (VDCCs). The aim of this study was to evaluate the involvement of Ca2+ entry via L-type CaV1.2 VDCCs in the processes of neuroinflammation and regeneration after brain injury. Methods: TBI was performed on male Wistar rats by sensorimotor cortex ablation (SCA) at the following coordinates: 2 mm anterior and 4 mm posterior to bregma, and 4 mm lateral from the midline. Temporal and cellular pattern of CaV1.2 expression was followed at different time points post-injury (2, 7, 14, 30 dpi) using double immunofluorescence staining with specific markers. Results: Upregulation of CaV1.2 expression was detected on reactive astrocytes and astrocytic processes that form glial scar around the lesion site, on subset of proinflammatory microglia/macrophages and neutrophils surrounding the lesion cavity. Interestingly, presence of CaV1.2+ cells was detected in the migratory pathway, consisted of DCX+ progenitors, extending from subventricular zone up to the lesion site. Furthermore, CaV1.2+/DCX+ newborn neurons were detected in subgranular layer of hippocampal dentate gyrus. Conclusions: We concluded that L-type CaV1.2 calcium channel has an important role in the regulation of processes of neuroinflammation, neuroregeneration and neurogenesis, pointing to the complexity of intercellular regulation of Ca2+ homeostasis after brain injury. Consequently, modulation of CaV1.2 channels expression may be potential target for the treatment of brain injury.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "L-type Calcium Channels Involvement in the Regulation of Neuroinflammation and Neuroregeneration After Brain Injury",
pages = "487",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5989"
}

Dacić, S., Božić, I., Jeremić, R., Bjelobaba, I., Lavrnja, I., Savić, D., Rakić, L., Stojiljković, M.,& Peković, S.. (2019). L-type Calcium Channels Involvement in the Regulation of Neuroinflammation and Neuroregeneration After Brain Injury. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 487.
https://hdl.handle.net/21.15107/rcub_ibiss_5989

Dacić S, Božić I, Jeremić R, Bjelobaba I, Lavrnja I, Savić D, Rakić L, Stojiljković M, Peković S. L-type Calcium Channels Involvement in the Regulation of Neuroinflammation and Neuroregeneration After Brain Injury. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:487.
https://hdl.handle.net/21.15107/rcub_ibiss_5989 .

Dacić, Sanja, Božić, Iva, Jeremić, Rada, Bjelobaba, Ivana, Lavrnja, Irena, Savić, Danijela, Rakić, Ljubisav, Stojiljković, Mirjana, Peković, Sanja, "L-type Calcium Channels Involvement in the Regulation of Neuroinflammation and Neuroregeneration After Brain Injury" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):487,
https://hdl.handle.net/21.15107/rcub_ibiss_5989 .

TY  - CONF
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Lavrnja, Irena
AU  - Savić, Danijela
AU  - Jakovljević, Marija
AU  - Peković, Sanja
AU  - Bjelobaba, Ivana
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5972
AB  - Aims: Multiple sclerosis (MS) is a chronic neuroinflammatory disease, more common in women than in men. Because the effects of MS on hypothalamo-pituitary-gonadal axis haven’t been completely elucidated, our aim was to investigate the impact of experimental autoimmune encephalomyelitis (EAE) on reproductive functions in rats. Methods: EAE was actively induced in Dark-Agouti rats of both sexes. Disease symptoms, weight changes, and estrous cycle phase were assessed daily. The animals were sacrificed at the onset, peak, and end of EAE. Hypothalamic, pituitary and gonadal tissues were dissected for qRT-PCR and/or protein extraction. Blood was collected for hormone measurements. In separate experiments, animals at the peak of EAE and naïve controls received an injection of a GnRH analogue - buserelin. Results: Our results suggest hypothalamic neuroinflammation in both sexes; upregulation of mRNA for several genes was registered during EAE. Hypothalamic expression of Kiss1 and Gnrh, as well as pituitary expression of Lhb, Fshb and Gnrhr mRNA, were affected differently in males and females. LH levels drop transiently following the course of EAE, coinciding with the arrest in diestrus in females and a drop in testosterone levels in males. Buserelin increased LH levels in both sexes. Additionally, StAR – a protein with a critical role in steroid hormone biosynthesis, had an opposite pattern of expression in ovaries and testicular interstitial cells during the disease, both on mRNA and protein level. Conclusion: Our data indicate that EAE noticeably affects the regulation of HPG axis. Further analyses are needed to explore the details of this phenomenon.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Experimental Autoimmune Encephalomyelitis Disturbs the Regulation of HPG Axis in Rats of Both Sexes
SP  - 293
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5972
ER  - 

@conference{
author = "Milošević, Ana and Janjić, Marija and Lavrnja, Irena and Savić, Danijela and Jakovljević, Marija and Peković, Sanja and Bjelobaba, Ivana",
year = "2019",
abstract = "Aims: Multiple sclerosis (MS) is a chronic neuroinflammatory disease, more common in women than in men. Because the effects of MS on hypothalamo-pituitary-gonadal axis haven’t been completely elucidated, our aim was to investigate the impact of experimental autoimmune encephalomyelitis (EAE) on reproductive functions in rats. Methods: EAE was actively induced in Dark-Agouti rats of both sexes. Disease symptoms, weight changes, and estrous cycle phase were assessed daily. The animals were sacrificed at the onset, peak, and end of EAE. Hypothalamic, pituitary and gonadal tissues were dissected for qRT-PCR and/or protein extraction. Blood was collected for hormone measurements. In separate experiments, animals at the peak of EAE and naïve controls received an injection of a GnRH analogue - buserelin. Results: Our results suggest hypothalamic neuroinflammation in both sexes; upregulation of mRNA for several genes was registered during EAE. Hypothalamic expression of Kiss1 and Gnrh, as well as pituitary expression of Lhb, Fshb and Gnrhr mRNA, were affected differently in males and females. LH levels drop transiently following the course of EAE, coinciding with the arrest in diestrus in females and a drop in testosterone levels in males. Buserelin increased LH levels in both sexes. Additionally, StAR – a protein with a critical role in steroid hormone biosynthesis, had an opposite pattern of expression in ovaries and testicular interstitial cells during the disease, both on mRNA and protein level. Conclusion: Our data indicate that EAE noticeably affects the regulation of HPG axis. Further analyses are needed to explore the details of this phenomenon.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Experimental Autoimmune Encephalomyelitis Disturbs the Regulation of HPG Axis in Rats of Both Sexes",
pages = "293",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5972"
}

Milošević, A., Janjić, M., Lavrnja, I., Savić, D., Jakovljević, M., Peković, S.,& Bjelobaba, I.. (2019). Experimental Autoimmune Encephalomyelitis Disturbs the Regulation of HPG Axis in Rats of Both Sexes. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society., 293.
https://hdl.handle.net/21.15107/rcub_ibiss_5972

Milošević A, Janjić M, Lavrnja I, Savić D, Jakovljević M, Peković S, Bjelobaba I. Experimental Autoimmune Encephalomyelitis Disturbs the Regulation of HPG Axis in Rats of Both Sexes. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:293.
https://hdl.handle.net/21.15107/rcub_ibiss_5972 .

Milošević, Ana, Janjić, Marija, Lavrnja, Irena, Savić, Danijela, Jakovljević, Marija, Peković, Sanja, Bjelobaba, Ivana, "Experimental Autoimmune Encephalomyelitis Disturbs the Regulation of HPG Axis in Rats of Both Sexes" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):293,
https://hdl.handle.net/21.15107/rcub_ibiss_5972 .

TY  - CONF
AU  - Laketa, Danijela
AU  - Jakovljević, Marija
AU  - Božić, Iva
AU  - Bjelobaba, Ivana
AU  - Savić, Danijela
AU  - Peković, Sanja
AU  - Nedeljković, Nadežda
AU  - Lavrnja, Irena
PY  - 2019
UR  - https://biore.bio.bg.ac.rs/handle/123456789/2265
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5893
AB  - Ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1/CD39) is the main ATP- and ADPdegrading
enzyme in extracellular fluid of the central nervous system. In the hydrolysis cascade
NTPDase1 removes ATP and ADP and produces AMP, which is hydrolysed by ecto-5'-nucleotidase to
adenosine. During neuroinflammation, increased extracellular ATP levels exert proinflammatory effects
at microglia as resident immune cells, while adenosine effects are antiinflammatory. Literature data
indicate involvement of purinergic signaling in experimental autoimmune encephalomyelitis (EAE), while
decreased number of NTPDase1/CD39+ regulatory T-cells was evidenced in multiple sclerosis.
Downregulation of NTPDase1 expression was observed in proinflammatory activation phenotype of
macrophages. However, data on the role of NTPDase1 on glial cells in neuroinflammation are still
scarce. We have shown increase in ATP-, ADP- and AMP-hydrolysis, together with upregulated mRNA
and protein expression of NTPDase1 in lumbar spinal cord, correlated to the disease course during EAE.
In this study we aimed to explore contribution of particular cell subsets to the observed changes in
NTPDase1 expression.
Acute monophasic EAE was induced in female rats of Dark Agouti strain by active immunization with a
mixture of spinal cord homogenate in complete Freund’s adjuvant. Immunized animals were sacrificed at
the onset, peak and end of symptoms, while naïve animals were used as control. Significant increase of
NTPDase1 immunofluorescence in lumbar spinal cord cross-sections was related to prominent infiltrates
at the peak of EAE and increased expression of NTPDase1 among isolated mononuclear cells. Analysis
of triple-labeled Arginase1/NTPDase1/Iba1 and iNOS/NTPDase1/Iba1 immunofluorescent micrographs
showed prevalent contribution of Arginase1+ microglia in comparison to iNOS+ microglia in NTPDase1
immunofluorescence, at the peak of EAE. Further studies are needed to reveal possible association of
NTPDase1 with antiinflammatory phenotype in microglia.
PB  - German Neuroscience Society
C3  - Proceedings: 13th Göttingen Meeting of the German Neuroscience Society 2019 and 37th Göttingen Neurobiology Conference; 2019 Mar 20-23; Göttingen, Germany
T1  - Microglia-related increase in NTPDase1 expression during EAE
SP  - T12-5B
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5893
ER  - 

@conference{
author = "Laketa, Danijela and Jakovljević, Marija and Božić, Iva and Bjelobaba, Ivana and Savić, Danijela and Peković, Sanja and Nedeljković, Nadežda and Lavrnja, Irena",
year = "2019",
abstract = "Ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1/CD39) is the main ATP- and ADPdegrading
enzyme in extracellular fluid of the central nervous system. In the hydrolysis cascade
NTPDase1 removes ATP and ADP and produces AMP, which is hydrolysed by ecto-5'-nucleotidase to
adenosine. During neuroinflammation, increased extracellular ATP levels exert proinflammatory effects
at microglia as resident immune cells, while adenosine effects are antiinflammatory. Literature data
indicate involvement of purinergic signaling in experimental autoimmune encephalomyelitis (EAE), while
decreased number of NTPDase1/CD39+ regulatory T-cells was evidenced in multiple sclerosis.
Downregulation of NTPDase1 expression was observed in proinflammatory activation phenotype of
macrophages. However, data on the role of NTPDase1 on glial cells in neuroinflammation are still
scarce. We have shown increase in ATP-, ADP- and AMP-hydrolysis, together with upregulated mRNA
and protein expression of NTPDase1 in lumbar spinal cord, correlated to the disease course during EAE.
In this study we aimed to explore contribution of particular cell subsets to the observed changes in
NTPDase1 expression.
Acute monophasic EAE was induced in female rats of Dark Agouti strain by active immunization with a
mixture of spinal cord homogenate in complete Freund’s adjuvant. Immunized animals were sacrificed at
the onset, peak and end of symptoms, while naïve animals were used as control. Significant increase of
NTPDase1 immunofluorescence in lumbar spinal cord cross-sections was related to prominent infiltrates
at the peak of EAE and increased expression of NTPDase1 among isolated mononuclear cells. Analysis
of triple-labeled Arginase1/NTPDase1/Iba1 and iNOS/NTPDase1/Iba1 immunofluorescent micrographs
showed prevalent contribution of Arginase1+ microglia in comparison to iNOS+ microglia in NTPDase1
immunofluorescence, at the peak of EAE. Further studies are needed to reveal possible association of
NTPDase1 with antiinflammatory phenotype in microglia.",
publisher = "German Neuroscience Society",
journal = "Proceedings: 13th Göttingen Meeting of the German Neuroscience Society 2019 and 37th Göttingen Neurobiology Conference; 2019 Mar 20-23; Göttingen, Germany",
title = "Microglia-related increase in NTPDase1 expression during EAE",
pages = "T12-5B",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5893"
}

Laketa, D., Jakovljević, M., Božić, I., Bjelobaba, I., Savić, D., Peković, S., Nedeljković, N.,& Lavrnja, I.. (2019). Microglia-related increase in NTPDase1 expression during EAE. in Proceedings: 13th Göttingen Meeting of the German Neuroscience Society 2019 and 37th Göttingen Neurobiology Conference; 2019 Mar 20-23; Göttingen, Germany
German Neuroscience Society., T12-5B.
https://hdl.handle.net/21.15107/rcub_ibiss_5893

Laketa D, Jakovljević M, Božić I, Bjelobaba I, Savić D, Peković S, Nedeljković N, Lavrnja I. Microglia-related increase in NTPDase1 expression during EAE. in Proceedings: 13th Göttingen Meeting of the German Neuroscience Society 2019 and 37th Göttingen Neurobiology Conference; 2019 Mar 20-23; Göttingen, Germany. 2019;:T12-5B.
https://hdl.handle.net/21.15107/rcub_ibiss_5893 .

Laketa, Danijela, Jakovljević, Marija, Božić, Iva, Bjelobaba, Ivana, Savić, Danijela, Peković, Sanja, Nedeljković, Nadežda, Lavrnja, Irena, "Microglia-related increase in NTPDase1 expression during EAE" in Proceedings: 13th Göttingen Meeting of the German Neuroscience Society 2019 and 37th Göttingen Neurobiology Conference; 2019 Mar 20-23; Göttingen, Germany (2019):T12-5B,
https://hdl.handle.net/21.15107/rcub_ibiss_5893 .

TY  - JOUR
AU  - Ehmedah, Adil
AU  - Nedeljković, Predrag
AU  - Dacic, Sanja
AU  - Repac, Jelena
AU  - Drašković Pavlović, Biljana
AU  - Vučević, Dragana
AU  - Peković, Sanja
AU  - Božić Nedeljković, Biljana
PY  - 2019
UR  - https://www.mdpi.com/1420-3049/24/24/4615
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3578
AB  - Peripheral nerve injury (PNI) leads to a series of cellular and molecular events necessary for axon regeneration and reinnervation of target tissues, among which inflammation is crucial for the orchestration of all these processes. Macrophage activation underlies the pathogenesis of PNI and is characterized by morphological/phenotype transformation from proinflammatory (M1) to an anti-inflammatory (M2) type with different functions in the inflammatory and reparative process. The aim of this study was to evaluate influence of the vitamin B (B1, B2, B3, B5, B6, and B12) complex on the process of neuroinflammation that is in part regulated by l-type CaV1.2 calcium channels. A controlled transection of the motor branch of the femoral peripheral nerve was used as an experimental model. Animals were sacrificed after 1, 3, 7, and 14 injections of vitamin B complex. Isolated nerves were used for immunofluorescence analysis. Treatment with vitamin B complex decreased expression of proinflammatory and increased expression of anti-inflammatory cytokines, thus contributing to the resolution of neuroinflammation. In parallel, B vitamins decreased the number of M1 macrophages that expressed the CaV1.2 channel, and increased the number of M2 macrophages that expressed this channel, suggesting their role in M1/M2 transition after PNI. In conclusion, B vitamins had the potential for treatment of neuroinflammation and neuroregeneration and thereby might be an effective therapy for PNI in humans.
PB  - Multidisciplinary Digital Publishing Institute
T2  - Molecules (Basel, Switzerland)
T1  - Vitamin B Complex Treatment Attenuates Local Inflammation after Peripheral Nerve Injury.
IS  - 24
VL  - 24
DO  - 10.3390/molecules24244615
SP  - 4615
ER  - 

@article{
author = "Ehmedah, Adil and Nedeljković, Predrag and Dacic, Sanja and Repac, Jelena and Drašković Pavlović, Biljana and Vučević, Dragana and Peković, Sanja and Božić Nedeljković, Biljana",
year = "2019",
abstract = "Peripheral nerve injury (PNI) leads to a series of cellular and molecular events necessary for axon regeneration and reinnervation of target tissues, among which inflammation is crucial for the orchestration of all these processes. Macrophage activation underlies the pathogenesis of PNI and is characterized by morphological/phenotype transformation from proinflammatory (M1) to an anti-inflammatory (M2) type with different functions in the inflammatory and reparative process. The aim of this study was to evaluate influence of the vitamin B (B1, B2, B3, B5, B6, and B12) complex on the process of neuroinflammation that is in part regulated by l-type CaV1.2 calcium channels. A controlled transection of the motor branch of the femoral peripheral nerve was used as an experimental model. Animals were sacrificed after 1, 3, 7, and 14 injections of vitamin B complex. Isolated nerves were used for immunofluorescence analysis. Treatment with vitamin B complex decreased expression of proinflammatory and increased expression of anti-inflammatory cytokines, thus contributing to the resolution of neuroinflammation. In parallel, B vitamins decreased the number of M1 macrophages that expressed the CaV1.2 channel, and increased the number of M2 macrophages that expressed this channel, suggesting their role in M1/M2 transition after PNI. In conclusion, B vitamins had the potential for treatment of neuroinflammation and neuroregeneration and thereby might be an effective therapy for PNI in humans.",
publisher = "Multidisciplinary Digital Publishing Institute",
journal = "Molecules (Basel, Switzerland)",
title = "Vitamin B Complex Treatment Attenuates Local Inflammation after Peripheral Nerve Injury.",
number = "24",
volume = "24",
doi = "10.3390/molecules24244615",
pages = "4615"
}

Ehmedah, A., Nedeljković, P., Dacic, S., Repac, J., Drašković Pavlović, B., Vučević, D., Peković, S.,& Božić Nedeljković, B.. (2019). Vitamin B Complex Treatment Attenuates Local Inflammation after Peripheral Nerve Injury.. in Molecules (Basel, Switzerland)
Multidisciplinary Digital Publishing Institute., 24(24), 4615.
https://doi.org/10.3390/molecules24244615

Ehmedah A, Nedeljković P, Dacic S, Repac J, Drašković Pavlović B, Vučević D, Peković S, Božić Nedeljković B. Vitamin B Complex Treatment Attenuates Local Inflammation after Peripheral Nerve Injury.. in Molecules (Basel, Switzerland). 2019;24(24):4615.
doi:10.3390/molecules24244615 .

Ehmedah, Adil, Nedeljković, Predrag, Dacic, Sanja, Repac, Jelena, Drašković Pavlović, Biljana, Vučević, Dragana, Peković, Sanja, Božić Nedeljković, Biljana, "Vitamin B Complex Treatment Attenuates Local Inflammation after Peripheral Nerve Injury." in Molecules (Basel, Switzerland), 24, no. 24 (2019):4615,
https://doi.org/10.3390/molecules24244615 . .

TY  - JOUR
AU  - Jakovljević, Marija
AU  - Lavrnja, Irena
AU  - Božić, Iva
AU  - Milošević, Ana
AU  - Bjelobaba, Ivana
AU  - Savić, Danijela
AU  - Sévigny, Jean
AU  - Peković, Sanja
AU  - Nedeljković, Nadežda
AU  - Laketa, Danijela
PY  - 2019
UR  - https://www.frontiersin.org/article/10.3389/fnins.2019.00410/full
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6498900
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3434
AB  - Purinergic signaling is critically involved in neuroinflammation associated with multiple sclerosis (MS) and its major inflammatory animal model, experimental autoimmune encephalomyelitis (EAE). Herein, we explored the expression of ectonucleoside triphosphate diphosphohydrolase1 (NTPDase1/CD39) in the spinal cord, at the onset (Eo), peak (Ep), and end (Ee) of EAE. Several-fold increase in mRNA and in NTPDase1 protein levels were observed at Eo and Ep. In situ hybridization combined with fluorescent immunohistochemistry showed that reactive microglia and infiltrated mononuclear cells mostly accounted for the observed increase. Colocalization analysis revealed that up to 80% of Iba1 immunoreactivity and ∼50% of CD68 immunoreactivity was colocalized with NTPDase1, while flow cytometric analysis revealed that ∼70% of mononuclear infiltrates were NTPDase1+ at Ep. Given the main role of NTPDase1 to degrade proinflammatory ATP, we hypothesized that the observed up-regulation of NTPDase1 may be associated with the transition between proinflammatory M1-like to neuroprotective M2-like phenotype of microglia/macrophages during EAE. Functional phenotype of reactive microglia/macrophages that overexpress NTPDase1 was assessed by multi-image colocalization analysis using iNOS and Arg1 as selective markers for M1 and M2 reactive states, respectively. At the peak of EAE NTPDase1 immunoreactivity showed much higher co-occurrence with Arg1 immunoreactivity in microglia and macrophages, compared to iNOS, implying its stronger association with M2-like reactive phenotype. Additionally, in ∼80% of CD68 positive cells NTPDase1 was coexpressed with Arg1 compared to negligible fraction coexpresing iNOS and ∼15% coexpresing both markers, additionally indicating prevalent association of NTPDase1 with M2-like microglial/macrophages phenotype at Ep. Together, our data suggest an association between NTPDase1 up-regulation by reactive microglia and infiltrated macrophages and their transition toward antiinflammatory phenotype in EAE.
T2  - Frontiers in Neuroscience
T1  - Induction of NTPDase1/CD39 by Reactive Microglia and Macrophages Is Associated With the Functional State During EAE.
VL  - 13
DO  - 10.3389/fnins.2019.00410
SP  - 410
ER  - 

@article{
author = "Jakovljević, Marija and Lavrnja, Irena and Božić, Iva and Milošević, Ana and Bjelobaba, Ivana and Savić, Danijela and Sévigny, Jean and Peković, Sanja and Nedeljković, Nadežda and Laketa, Danijela",
year = "2019",
abstract = "Purinergic signaling is critically involved in neuroinflammation associated with multiple sclerosis (MS) and its major inflammatory animal model, experimental autoimmune encephalomyelitis (EAE). Herein, we explored the expression of ectonucleoside triphosphate diphosphohydrolase1 (NTPDase1/CD39) in the spinal cord, at the onset (Eo), peak (Ep), and end (Ee) of EAE. Several-fold increase in mRNA and in NTPDase1 protein levels were observed at Eo and Ep. In situ hybridization combined with fluorescent immunohistochemistry showed that reactive microglia and infiltrated mononuclear cells mostly accounted for the observed increase. Colocalization analysis revealed that up to 80% of Iba1 immunoreactivity and ∼50% of CD68 immunoreactivity was colocalized with NTPDase1, while flow cytometric analysis revealed that ∼70% of mononuclear infiltrates were NTPDase1+ at Ep. Given the main role of NTPDase1 to degrade proinflammatory ATP, we hypothesized that the observed up-regulation of NTPDase1 may be associated with the transition between proinflammatory M1-like to neuroprotective M2-like phenotype of microglia/macrophages during EAE. Functional phenotype of reactive microglia/macrophages that overexpress NTPDase1 was assessed by multi-image colocalization analysis using iNOS and Arg1 as selective markers for M1 and M2 reactive states, respectively. At the peak of EAE NTPDase1 immunoreactivity showed much higher co-occurrence with Arg1 immunoreactivity in microglia and macrophages, compared to iNOS, implying its stronger association with M2-like reactive phenotype. Additionally, in ∼80% of CD68 positive cells NTPDase1 was coexpressed with Arg1 compared to negligible fraction coexpresing iNOS and ∼15% coexpresing both markers, additionally indicating prevalent association of NTPDase1 with M2-like microglial/macrophages phenotype at Ep. Together, our data suggest an association between NTPDase1 up-regulation by reactive microglia and infiltrated macrophages and their transition toward antiinflammatory phenotype in EAE.",
journal = "Frontiers in Neuroscience",
title = "Induction of NTPDase1/CD39 by Reactive Microglia and Macrophages Is Associated With the Functional State During EAE.",
volume = "13",
doi = "10.3389/fnins.2019.00410",
pages = "410"
}

Jakovljević, M., Lavrnja, I., Božić, I., Milošević, A., Bjelobaba, I., Savić, D., Sévigny, J., Peković, S., Nedeljković, N.,& Laketa, D.. (2019). Induction of NTPDase1/CD39 by Reactive Microglia and Macrophages Is Associated With the Functional State During EAE.. in Frontiers in Neuroscience, 13, 410.
https://doi.org/10.3389/fnins.2019.00410

Jakovljević M, Lavrnja I, Božić I, Milošević A, Bjelobaba I, Savić D, Sévigny J, Peković S, Nedeljković N, Laketa D. Induction of NTPDase1/CD39 by Reactive Microglia and Macrophages Is Associated With the Functional State During EAE.. in Frontiers in Neuroscience. 2019;13:410.
doi:10.3389/fnins.2019.00410 .

Jakovljević, Marija, Lavrnja, Irena, Božić, Iva, Milošević, Ana, Bjelobaba, Ivana, Savić, Danijela, Sévigny, Jean, Peković, Sanja, Nedeljković, Nadežda, Laketa, Danijela, "Induction of NTPDase1/CD39 by Reactive Microglia and Macrophages Is Associated With the Functional State During EAE." in Frontiers in Neuroscience, 13 (2019):410,
https://doi.org/10.3389/fnins.2019.00410 . .

TY  - JOUR
AU  - Bjelobaba, Ivana
AU  - Begović-Kuprešanin, Vesna
AU  - Peković, Sanja
AU  - Lavrnja, Irena
PY  - 2018
UR  - http://doi.wiley.com/10.1002/jnr.24224
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3010
AB  - Multiple sclerosis (MS) is a chronic, progressive disorder of the central nervous system (CNS) that affects more than two million people worldwide. Several animal models resemble MS pathology; the most employed are experimental autoimmune encephalomyelitis (EAE) and toxin- and/or virus-induced demyelination. In this review we will summarize our knowledge on the utility of different animal models in MS research. Although animal models cannot replicate the complexity and heterogeneity of the MS pathology, they have proved to be useful for the development of several drugs approved for treatment of MS patients. This review focuses on EAE because it represents both clinical and pathological features of MS. During the past decades, EAE has been effective in illuminating various pathological processes that occur during MS, including inflammation, CNS penetration, demyelination, axonopathy, and neuron loss mediated by immune cells.
T2  - Journal of Neuroscience Research
T1  - Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis.
IS  - 6
VL  - 96
DO  - 10.1002/jnr.24224
SP  - 1021
EP  - 1042
ER  - 

@article{
author = "Bjelobaba, Ivana and Begović-Kuprešanin, Vesna and Peković, Sanja and Lavrnja, Irena",
year = "2018",
abstract = "Multiple sclerosis (MS) is a chronic, progressive disorder of the central nervous system (CNS) that affects more than two million people worldwide. Several animal models resemble MS pathology; the most employed are experimental autoimmune encephalomyelitis (EAE) and toxin- and/or virus-induced demyelination. In this review we will summarize our knowledge on the utility of different animal models in MS research. Although animal models cannot replicate the complexity and heterogeneity of the MS pathology, they have proved to be useful for the development of several drugs approved for treatment of MS patients. This review focuses on EAE because it represents both clinical and pathological features of MS. During the past decades, EAE has been effective in illuminating various pathological processes that occur during MS, including inflammation, CNS penetration, demyelination, axonopathy, and neuron loss mediated by immune cells.",
journal = "Journal of Neuroscience Research",
title = "Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis.",
number = "6",
volume = "96",
doi = "10.1002/jnr.24224",
pages = "1021-1042"
}

Bjelobaba, I., Begović-Kuprešanin, V., Peković, S.,& Lavrnja, I.. (2018). Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis.. in Journal of Neuroscience Research, 96(6), 1021-1042.
https://doi.org/10.1002/jnr.24224

Bjelobaba I, Begović-Kuprešanin V, Peković S, Lavrnja I. Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis.. in Journal of Neuroscience Research. 2018;96(6):1021-1042.
doi:10.1002/jnr.24224 .

Bjelobaba, Ivana, Begović-Kuprešanin, Vesna, Peković, Sanja, Lavrnja, Irena, "Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis." in Journal of Neuroscience Research, 96, no. 6 (2018):1021-1042,
https://doi.org/10.1002/jnr.24224 . .

TY  - JOUR
AU  - Božić, Iva
AU  - Milošević, Katarina
AU  - Laketa, Danijela
AU  - Adžić, Marija
AU  - Jakovljević, Marija
AU  - Bjelobaba, Ivana
AU  - Savić, Danijela
AU  - Nedeljković, Nadežda
AU  - Peković, Sanja
AU  - Lavrnja, Irena
PY  - 2018
UR  - http://link.springer.com/10.1007/s11064-018-2509-8
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3027
AB  - Kv1.3 is a voltage gated potassium channel that has been implicated in pathophysiology of multiple sclerosis (MS). In the present study we investigated temporal and cellular expression pattern of this channel in the lumbar part of spinal cords of animals with experimental autoimmune encephalomyelitis (EAE), animal model of MS. EAE was actively induced in female Dark Agouti rats. Expression of Kv1.3 was analyzed at different time points of disease progression, at the onset, peak and end of EAE. We here show that Kv1.3 increased by several folds at the peak of EAE at both gene and protein level. Double immunofluorescence analyses demonstrated localization of Kv1.3 on activated microglia, macrophages, and reactive astrocytes around inflammatory lesions. In vitro experiments showed that pharmacological block of Kv1.3 in activated astrocytes suppresses the expression of proinflammatory mediators, suggesting a role of this channel in inflammation. Our results support the hypothesis that Kv1.3 may be a therapeutic target of interest for MS and add astrocytes to the list of cells whose activation would be suppressed by inhibiting Kv1.3 in inflammatory conditions.
T2  - Neurochemical Research
T1  - Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.
IS  - 5
VL  - 43
DO  - 10.1007/s11064-018-2509-8
SP  - 1020
EP  - 1034
ER  - 

@article{
author = "Božić, Iva and Milošević, Katarina and Laketa, Danijela and Adžić, Marija and Jakovljević, Marija and Bjelobaba, Ivana and Savić, Danijela and Nedeljković, Nadežda and Peković, Sanja and Lavrnja, Irena",
year = "2018",
abstract = "Kv1.3 is a voltage gated potassium channel that has been implicated in pathophysiology of multiple sclerosis (MS). In the present study we investigated temporal and cellular expression pattern of this channel in the lumbar part of spinal cords of animals with experimental autoimmune encephalomyelitis (EAE), animal model of MS. EAE was actively induced in female Dark Agouti rats. Expression of Kv1.3 was analyzed at different time points of disease progression, at the onset, peak and end of EAE. We here show that Kv1.3 increased by several folds at the peak of EAE at both gene and protein level. Double immunofluorescence analyses demonstrated localization of Kv1.3 on activated microglia, macrophages, and reactive astrocytes around inflammatory lesions. In vitro experiments showed that pharmacological block of Kv1.3 in activated astrocytes suppresses the expression of proinflammatory mediators, suggesting a role of this channel in inflammation. Our results support the hypothesis that Kv1.3 may be a therapeutic target of interest for MS and add astrocytes to the list of cells whose activation would be suppressed by inhibiting Kv1.3 in inflammatory conditions.",
journal = "Neurochemical Research",
title = "Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.",
number = "5",
volume = "43",
doi = "10.1007/s11064-018-2509-8",
pages = "1020-1034"
}

Božić, I., Milošević, K., Laketa, D., Adžić, M., Jakovljević, M., Bjelobaba, I., Savić, D., Nedeljković, N., Peković, S.,& Lavrnja, I.. (2018). Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.. in Neurochemical Research, 43(5), 1020-1034.
https://doi.org/10.1007/s11064-018-2509-8

Božić I, Milošević K, Laketa D, Adžić M, Jakovljević M, Bjelobaba I, Savić D, Nedeljković N, Peković S, Lavrnja I. Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.. in Neurochemical Research. 2018;43(5):1020-1034.
doi:10.1007/s11064-018-2509-8 .

Božić, Iva, Milošević, Katarina, Laketa, Danijela, Adžić, Marija, Jakovljević, Marija, Bjelobaba, Ivana, Savić, Danijela, Nedeljković, Nadežda, Peković, Sanja, Lavrnja, Irena, "Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis." in Neurochemical Research, 43, no. 5 (2018):1020-1034,
https://doi.org/10.1007/s11064-018-2509-8 . .

TY  - CONF
AU  - Savić, Danijela
AU  - Lavrnja, Irena
AU  - Bjelobaba, Ivana
AU  - Dacić, Sanja
AU  - Laketa, Danijela
AU  - Božić, Iva
AU  - Jakovljević, Marija
AU  - Nedeljković, Nadežda
AU  - Rakić, Ljubisav
AU  - Peković, Sanja
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5888
AB  - Ribavirin je purinski nukleozidni analog, otkriven pre više decenija i odobren kao lek protiv virusa hepatitisa C. Sa otkrićem direktnih antivirusnih agenasa, nastupila je revolucija u lečenju hepatitisa C, a terapijska uloga ribavirina je marginalizovana. Međutim, ribavirin ima širok spektar dejstva što je otvorilo mogućnost da se ovaj lek preusmeri ka tretmanu drugih oboljenja. Naime, osim što deluje antivirusno (inhibicija virusne RNK polimeraze i izazivanje letalne mutageneze) ribavirin je i inhibitor eukariotskog faktora za inicijaciju translacije e4E, što je zaslužno za njegov anti-tumorski efekat, pokazan u leukemiji i na ćelijama glioma. Njegova druga opšte poznata unutarćelijska meta jeste enzim inozin-5’-monofosfat dehidrogenaza (IMPDH), koji predstavlja ključni faktor u de novo sintezi guaninskih nukleotida. Ćelije koje se isključivo na ovaj način snabdevaju purinskim nukleotidima, kao što su aktivirani limfociti i neke proliferišuće ćelije, izuzetno su senzitivne na delovanje ribavirina. Inhibicija IMPDH odgovorna je za imunosupresivno i imunomodulatorno dejstvo ribavirina, pokazano u in vitro i in vivo modelima neuroinflamacije. Dakle, iako ribavirin gubi centralnu ulogu koju je imao u terapiji infekcije virusom hepatitisa C, njegova multipotentna priroda koja se ogleda u različitim mehanizmima delovanja, predstavlja potencijal za preusmeravanje ka novim terapijskim indikacijama, kao što su kancer ili multipla skleroza.
PB  - Belgrade: Serbian Biological Society
C3  - Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija
T1  - Preusmeravanje antivirusnog leka ribavirina ka novim terapijskim indikacijama: primer multiple skleroze i neoplastičnih transformacija
SP  - 146
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5888
ER  - 

@conference{
author = "Savić, Danijela and Lavrnja, Irena and Bjelobaba, Ivana and Dacić, Sanja and Laketa, Danijela and Božić, Iva and Jakovljević, Marija and Nedeljković, Nadežda and Rakić, Ljubisav and Peković, Sanja",
year = "2018",
abstract = "Ribavirin je purinski nukleozidni analog, otkriven pre više decenija i odobren kao lek protiv virusa hepatitisa C. Sa otkrićem direktnih antivirusnih agenasa, nastupila je revolucija u lečenju hepatitisa C, a terapijska uloga ribavirina je marginalizovana. Međutim, ribavirin ima širok spektar dejstva što je otvorilo mogućnost da se ovaj lek preusmeri ka tretmanu drugih oboljenja. Naime, osim što deluje antivirusno (inhibicija virusne RNK polimeraze i izazivanje letalne mutageneze) ribavirin je i inhibitor eukariotskog faktora za inicijaciju translacije e4E, što je zaslužno za njegov anti-tumorski efekat, pokazan u leukemiji i na ćelijama glioma. Njegova druga opšte poznata unutarćelijska meta jeste enzim inozin-5’-monofosfat dehidrogenaza (IMPDH), koji predstavlja ključni faktor u de novo sintezi guaninskih nukleotida. Ćelije koje se isključivo na ovaj način snabdevaju purinskim nukleotidima, kao što su aktivirani limfociti i neke proliferišuće ćelije, izuzetno su senzitivne na delovanje ribavirina. Inhibicija IMPDH odgovorna je za imunosupresivno i imunomodulatorno dejstvo ribavirina, pokazano u in vitro i in vivo modelima neuroinflamacije. Dakle, iako ribavirin gubi centralnu ulogu koju je imao u terapiji infekcije virusom hepatitisa C, njegova multipotentna priroda koja se ogleda u različitim mehanizmima delovanja, predstavlja potencijal za preusmeravanje ka novim terapijskim indikacijama, kao što su kancer ili multipla skleroza.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija",
title = "Preusmeravanje antivirusnog leka ribavirina ka novim terapijskim indikacijama: primer multiple skleroze i neoplastičnih transformacija",
pages = "146",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5888"
}

Savić, D., Lavrnja, I., Bjelobaba, I., Dacić, S., Laketa, D., Božić, I., Jakovljević, M., Nedeljković, N., Rakić, L.,& Peković, S.. (2018). Preusmeravanje antivirusnog leka ribavirina ka novim terapijskim indikacijama: primer multiple skleroze i neoplastičnih transformacija. in Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija
Belgrade: Serbian Biological Society., 146.
https://hdl.handle.net/21.15107/rcub_ibiss_5888

Savić D, Lavrnja I, Bjelobaba I, Dacić S, Laketa D, Božić I, Jakovljević M, Nedeljković N, Rakić L, Peković S. Preusmeravanje antivirusnog leka ribavirina ka novim terapijskim indikacijama: primer multiple skleroze i neoplastičnih transformacija. in Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija. 2018;:146.
https://hdl.handle.net/21.15107/rcub_ibiss_5888 .

Savić, Danijela, Lavrnja, Irena, Bjelobaba, Ivana, Dacić, Sanja, Laketa, Danijela, Božić, Iva, Jakovljević, Marija, Nedeljković, Nadežda, Rakić, Ljubisav, Peković, Sanja, "Preusmeravanje antivirusnog leka ribavirina ka novim terapijskim indikacijama: primer multiple skleroze i neoplastičnih transformacija" in Drugi kongres biologa Srbije; 2018 Sep 25-30; Kladovo, Srbija (2018):146,
https://hdl.handle.net/21.15107/rcub_ibiss_5888 .

TY  - CHAP
AU  - Savić, Danijela
AU  - Bjelobaba, Ivana
AU  - Peković, Sanja
AU  - Lavrnja, Irena
PY  - 2018
UR  - http://www.eurekaselect.com/node/164235
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3215
AB  - Discovered 45 years ago, ribavirin still proves useful as a broad-spectrum anti-viral drug against different RNA and DNA viruses. Although many cellular and molecular mechanisms of ribavirin action have been proposed during several decades of the extensive research, the complete spectrum of its actions is still not fully known. The direct mechanisms of ribavirin anti-viral action involve RNA polymerase inhibition and lethal mutagenesis. The main intracellular target of ribavirin action is inosine 5'-monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in a de novo synthesis of guanine nucleotides. The inhibition of IMPDH activity leads to depletion of the guanine nucleotide pool and the consequent attenuation of GTPdependent cellular processes, inducing cell cycle arrest, and the interruption of DNA and RNA synthesis. Since these processes are essential for the normal as well as mitogenic functions of all cells, the inhibition of IMPDH probably represents the central mechanism of ribavirin action, including its cytotoxic effect. Recent data suggest that ribavirin may also be effective as an anti-cancer drug. By inhibiting the eukaryotic translation initiation factor e4E (eIF4E), ribavirin impedes eIF4E-mediated oncogenic transformation. Additionally, immunomodulatory and immunosuppressive actions of ribavirin have been shown in different in vivo and in vitro models of neuroinflammation. Accumulating evidence points to important cell type-specific differences in response to ribavirin that may arise from cell specific variations in ribavirin metabolism, as well as the functional status of targeted cells. This chapter reviews the antiviral, anticancer and anti-inflammatory activities of ribavirin and its metabolites, and discusses the possible mechanisms of action.
PB  - Bentham Science Publishers
T2  - Frontiers in Drug Design & Discovery. Volume 9.
T1  - Ribavirin Against Viral, Neoplastic and Inflammatory Diseases: Focus on Mechanisms of Action
DO  - 10.2174/9781681085821118090006
SP  - 113
EP  - 175
ER  - 

@inbook{
author = "Savić, Danijela and Bjelobaba, Ivana and Peković, Sanja and Lavrnja, Irena",
year = "2018",
abstract = "Discovered 45 years ago, ribavirin still proves useful as a broad-spectrum anti-viral drug against different RNA and DNA viruses. Although many cellular and molecular mechanisms of ribavirin action have been proposed during several decades of the extensive research, the complete spectrum of its actions is still not fully known. The direct mechanisms of ribavirin anti-viral action involve RNA polymerase inhibition and lethal mutagenesis. The main intracellular target of ribavirin action is inosine 5'-monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in a de novo synthesis of guanine nucleotides. The inhibition of IMPDH activity leads to depletion of the guanine nucleotide pool and the consequent attenuation of GTPdependent cellular processes, inducing cell cycle arrest, and the interruption of DNA and RNA synthesis. Since these processes are essential for the normal as well as mitogenic functions of all cells, the inhibition of IMPDH probably represents the central mechanism of ribavirin action, including its cytotoxic effect. Recent data suggest that ribavirin may also be effective as an anti-cancer drug. By inhibiting the eukaryotic translation initiation factor e4E (eIF4E), ribavirin impedes eIF4E-mediated oncogenic transformation. Additionally, immunomodulatory and immunosuppressive actions of ribavirin have been shown in different in vivo and in vitro models of neuroinflammation. Accumulating evidence points to important cell type-specific differences in response to ribavirin that may arise from cell specific variations in ribavirin metabolism, as well as the functional status of targeted cells. This chapter reviews the antiviral, anticancer and anti-inflammatory activities of ribavirin and its metabolites, and discusses the possible mechanisms of action.",
publisher = "Bentham Science Publishers",
journal = "Frontiers in Drug Design & Discovery. Volume 9.",
booktitle = "Ribavirin Against Viral, Neoplastic and Inflammatory Diseases: Focus on Mechanisms of Action",
doi = "10.2174/9781681085821118090006",
pages = "113-175"
}

Savić, D., Bjelobaba, I., Peković, S.,& Lavrnja, I.. (2018). Ribavirin Against Viral, Neoplastic and Inflammatory Diseases: Focus on Mechanisms of Action. in Frontiers in Drug Design & Discovery. Volume 9.
Bentham Science Publishers., 113-175.
https://doi.org/10.2174/9781681085821118090006

Savić D, Bjelobaba I, Peković S, Lavrnja I. Ribavirin Against Viral, Neoplastic and Inflammatory Diseases: Focus on Mechanisms of Action. in Frontiers in Drug Design & Discovery. Volume 9.. 2018;:113-175.
doi:10.2174/9781681085821118090006 .

Savić, Danijela, Bjelobaba, Ivana, Peković, Sanja, Lavrnja, Irena, "Ribavirin Against Viral, Neoplastic and Inflammatory Diseases: Focus on Mechanisms of Action" in Frontiers in Drug Design & Discovery. Volume 9. (2018):113-175,
https://doi.org/10.2174/9781681085821118090006 . .

TY  - JOUR
AU  - Lavrnja, Irena
AU  - Smiljanić, Kosara
AU  - Savić, Danijela
AU  - Mladenović, Aleksandra
AU  - Milošević, Katarina
AU  - Kanazir, Selma
AU  - Peković, Sanja
PY  - 2017
UR  - http://www.nature.com/articles/s41598-017-02638-8
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2760
AB  - Increased evidence suggests that dysregulation of cholesterol metabolism may be a key event contributing to progression of multiple sclerosis (MS). Using an experimental autoimmune encephalomyelitis (EAE) model of MS we revealed specific changes in the mRNA and protein expression of key molecules involved in the maintaining of cholesterol homeostasis in the rat spinal cord: 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46A1) during the course of disease. The presence of myelin lipid debris was seen only at the peak of EAE in demyelination loci being efficiently removed during the recovery period. Since CYP46A1 is responsible for removal of cholesterol excess, we performed a detailed profiling of CYP46A1 expression and revealed regional and temporal specificities in its distribution. Double immunofluorescence staining demonstrated CYP46A1 localization with neurons, infiltrated macrophages, microglia and astrocytes in the areas of demyelination, suggesting that these cells play a role in cholesterol turnover in EAE. We propose that alterations in the regulation of cholesterol metabolism at the onset and peak of EAE may add to the progression of disease, while during the recovery period may have beneficial effects contributing to the regeneration of myelin sheath and restoration of neuronal function.
T2  - Scientific Reports
T1  - Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord
IS  - 1
VL  - 7
DO  - 10.1038/s41598-017-02638-8
SP  - 2702
EP  - 2702
ER  - 

@article{
author = "Lavrnja, Irena and Smiljanić, Kosara and Savić, Danijela and Mladenović, Aleksandra and Milošević, Katarina and Kanazir, Selma and Peković, Sanja",
year = "2017",
abstract = "Increased evidence suggests that dysregulation of cholesterol metabolism may be a key event contributing to progression of multiple sclerosis (MS). Using an experimental autoimmune encephalomyelitis (EAE) model of MS we revealed specific changes in the mRNA and protein expression of key molecules involved in the maintaining of cholesterol homeostasis in the rat spinal cord: 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46A1) during the course of disease. The presence of myelin lipid debris was seen only at the peak of EAE in demyelination loci being efficiently removed during the recovery period. Since CYP46A1 is responsible for removal of cholesterol excess, we performed a detailed profiling of CYP46A1 expression and revealed regional and temporal specificities in its distribution. Double immunofluorescence staining demonstrated CYP46A1 localization with neurons, infiltrated macrophages, microglia and astrocytes in the areas of demyelination, suggesting that these cells play a role in cholesterol turnover in EAE. We propose that alterations in the regulation of cholesterol metabolism at the onset and peak of EAE may add to the progression of disease, while during the recovery period may have beneficial effects contributing to the regeneration of myelin sheath and restoration of neuronal function.",
journal = "Scientific Reports",
title = "Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord",
number = "1",
volume = "7",
doi = "10.1038/s41598-017-02638-8",
pages = "2702-2702"
}

Lavrnja, I., Smiljanić, K., Savić, D., Mladenović, A., Milošević, K., Kanazir, S.,& Peković, S.. (2017). Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord. in Scientific Reports, 7(1), 2702-2702.
https://doi.org/10.1038/s41598-017-02638-8

Lavrnja I, Smiljanić K, Savić D, Mladenović A, Milošević K, Kanazir S, Peković S. Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord. in Scientific Reports. 2017;7(1):2702-2702.
doi:10.1038/s41598-017-02638-8 .

Lavrnja, Irena, Smiljanić, Kosara, Savić, Danijela, Mladenović, Aleksandra, Milošević, Katarina, Kanazir, Selma, Peković, Sanja, "Expression profiles of cholesterol metabolism-related genes are altered during development of experimental autoimmune encephalomyelitis in the rat spinal cord" in Scientific Reports, 7, no. 1 (2017):2702-2702,
https://doi.org/10.1038/s41598-017-02638-8 . .

TY  - CONF
AU  - Laketa, Danijela
AU  - Josipović, Nataša
AU  - Lavrnja, Irena
AU  - Bjelobaba, Ivana
AU  - Jakovljević, Marija
AU  - Božić, Iva
AU  - Savić, Danijela
AU  - Dacić, Sanja
AU  - Peković, Sanja
AU  - Nedeljković, Nadežda
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5988
AB  - Introduction. Ecto-5'–nucleotidase (eN) catalyzes terminal step of extracellular ATP hydrolysis, producing anti-inflammatory adenosine. We reported significantly increased eN activity in lumbar spinal cord during experimental autoimmune encephalomyelitis (EAE), together with increased protein expression connected mainly with reactive astrocytes and appearance of new isoform at ~75kDa at the peak of the disease, besides usual ~71kDa isoform. Since eN is glycoprotein with five potential N-glycosylation sites and 
redicted molecular weight of 57-59 kDa, we hypothesized that occurrence of second isoform during EAE is due to changes in glycosylation pattern, possibly affecting kinetic properties of the enzyme. Methods. Lumbar parts of the spinal cords were obtained from Dark Agouti rats at the onset (Eo), peak (Ep) and the end of symptoms (Er) during EAE and from naïve control animals (C). Results. We here report significant changes of kinetic properties regarding AMP-hydrolysis during EAE, with almost 50% increase of maximal velocity at Ep (92.35±1.86nmolPi/min/mg) and Er (90.68±2.17nmolPi/min/mg), compared to C, whilst Km increased double at Ep (0.041±0.003mmol/l). Enzymatic deglycosylation caused triple decrease of Vmax (33.6±1.8nmolPi/mg/min) at Ep, and double decrease of Km (0.022±0.008mmol/l), whilst immunoblot
probed with anti-eN antibody revealed triple protein band at ~60kDa at all investigated time-points. Conclusion. Our results show that changes of kinetic properties during EAE, at least partially, are governed by modification of glycosylation pattern. Also, appearance of new isoform at the peak of EAE is direct consequence of glycosylation changes. In summary, besides gene and protein expression changes of eN, glycosylation might be additional route of inflammation control conducted by astrocytes.
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  - Appearance of second ecto-5'-nucleotidase isoform during experimental autoimmune encephalomyelitis is caused by changes in glycosylation pattern
SP  - 70
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5988
ER  - 

@conference{
author = "Laketa, Danijela and Josipović, Nataša and Lavrnja, Irena and Bjelobaba, Ivana and Jakovljević, Marija and Božić, Iva and Savić, Danijela and Dacić, Sanja and Peković, Sanja and Nedeljković, Nadežda",
year = "2017",
abstract = "Introduction. Ecto-5'–nucleotidase (eN) catalyzes terminal step of extracellular ATP hydrolysis, producing anti-inflammatory adenosine. We reported significantly increased eN activity in lumbar spinal cord during experimental autoimmune encephalomyelitis (EAE), together with increased protein expression connected mainly with reactive astrocytes and appearance of new isoform at ~75kDa at the peak of the disease, besides usual ~71kDa isoform. Since eN is glycoprotein with five potential N-glycosylation sites and 
redicted molecular weight of 57-59 kDa, we hypothesized that occurrence of second isoform during EAE is due to changes in glycosylation pattern, possibly affecting kinetic properties of the enzyme. Methods. Lumbar parts of the spinal cords were obtained from Dark Agouti rats at the onset (Eo), peak (Ep) and the end of symptoms (Er) during EAE and from naïve control animals (C). Results. We here report significant changes of kinetic properties regarding AMP-hydrolysis during EAE, with almost 50% increase of maximal velocity at Ep (92.35±1.86nmolPi/min/mg) and Er (90.68±2.17nmolPi/min/mg), compared to C, whilst Km increased double at Ep (0.041±0.003mmol/l). Enzymatic deglycosylation caused triple decrease of Vmax (33.6±1.8nmolPi/mg/min) at Ep, and double decrease of Km (0.022±0.008mmol/l), whilst immunoblot
probed with anti-eN antibody revealed triple protein band at ~60kDa at all investigated time-points. Conclusion. Our results show that changes of kinetic properties during EAE, at least partially, are governed by modification of glycosylation pattern. Also, appearance of new isoform at the peak of EAE is direct consequence of glycosylation changes. In summary, besides gene and protein expression changes of eN, glycosylation might be additional route of inflammation control conducted by astrocytes.",
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 = "Appearance of second ecto-5'-nucleotidase isoform during experimental autoimmune encephalomyelitis is caused by changes in glycosylation pattern",
pages = "70",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5988"
}

Laketa, D., Josipović, N., Lavrnja, I., Bjelobaba, I., Jakovljević, M., Božić, I., Savić, D., Dacić, S., Peković, S.,& Nedeljković, N.. (2017). Appearance of second ecto-5'-nucleotidase isoform during experimental autoimmune encephalomyelitis is caused by changes in glycosylation pattern. in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 70.
https://hdl.handle.net/21.15107/rcub_ibiss_5988

Laketa D, Josipović N, Lavrnja I, Bjelobaba I, Jakovljević M, Božić I, Savić D, Dacić S, Peković S, Nedeljković N. Appearance of second ecto-5'-nucleotidase isoform during experimental autoimmune encephalomyelitis is caused by changes in glycosylation pattern. in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia. 2017;:70.
https://hdl.handle.net/21.15107/rcub_ibiss_5988 .

Laketa, Danijela, Josipović, Nataša, Lavrnja, Irena, Bjelobaba, Ivana, Jakovljević, Marija, Božić, Iva, Savić, Danijela, Dacić, Sanja, Peković, Sanja, Nedeljković, Nadežda, "Appearance of second ecto-5'-nucleotidase isoform during experimental autoimmune encephalomyelitis is caused by changes in glycosylation pattern" in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia (2017):70,
https://hdl.handle.net/21.15107/rcub_ibiss_5988 .