TY  - JOUR
AU  - Perić, Ivana
AU  - Costina, Victor
AU  - Gass, Peter
AU  - Findeisen, Peter
AU  - Filipović, Dragana
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9771
AB  - The susceptibility of an individual to chronic social isolation (CSIS) stress may cause major depression (MD) whereby some individuals are resistant to the stress. Recent studies relate MD with altered expression of synaptic proteins in specific brain regions. To explore the neurobiological underpinnings and identify candidate biomarkers of susceptibility or resilience to CSIS, a comparative proteomic approach was used to map hippocampal synaptic protein alterations of rats exposed to 6 weeks of CSIS, an animal model of depression. This model generates two stress-response phenotypes: CSIS-sensitive (depressive-like behaviour) and CSIS-resilience assessed by means of sucrose preference and forced swim tests. Our aim was to characterize the synaptoproteome changes representative of potential long-term changes in protein expression underlying susceptibility or resilience to stress. Proteomic data showed increased expression of glycolytic enzymes, the energy-related mitochondrial proteins, actin cytoskeleton, signalling transduction and synaptic transmission proteins in CSIS-sensitive rats. Protein levels of glutamate-related enzymes such as glutamate dehydrogenase and glutamine synthetase were also increased. CSIS-resilient rats showed similar proteome changes, however with a weaker increase compared to CSIS-sensitive rats. The main difference was observed in the level of protein expression of vesicle-mediated transport proteins. Nonetheless, only few proteins were uniquely up-regulated in the CSIS-resilient rats, whereby Cytochrome b-c1 complex subunit 2, mitochondrial (Uqcrc2) and Voltage-dependent anion-selective channel protein 1 (Vdac1) were uniquely down-regulated. Identified altered activated pathways and potential protein biomarkers may help us better understand the molecular mechanisms underlying synaptic neurotransmission in MD or resilience, crucial for development of new therapeutics. © 2020 Elsevier Inc.
T2  - Brain Research Bulletin
T1  - Hippocampal synaptoproteomic changes of susceptibility and resilience of male rats to chronic social isolation
VL  - 166
SP  - 128
EP  - 141
DO  - 10.1016/j.brainresbull.2020.11.013
ER  - 

@article{
author = "Perić, Ivana and Costina, Victor and Gass, Peter and Findeisen, Peter and Filipović, Dragana",
year = "2021",
abstract = "The susceptibility of an individual to chronic social isolation (CSIS) stress may cause major depression (MD) whereby some individuals are resistant to the stress. Recent studies relate MD with altered expression of synaptic proteins in specific brain regions. To explore the neurobiological underpinnings and identify candidate biomarkers of susceptibility or resilience to CSIS, a comparative proteomic approach was used to map hippocampal synaptic protein alterations of rats exposed to 6 weeks of CSIS, an animal model of depression. This model generates two stress-response phenotypes: CSIS-sensitive (depressive-like behaviour) and CSIS-resilience assessed by means of sucrose preference and forced swim tests. Our aim was to characterize the synaptoproteome changes representative of potential long-term changes in protein expression underlying susceptibility or resilience to stress. Proteomic data showed increased expression of glycolytic enzymes, the energy-related mitochondrial proteins, actin cytoskeleton, signalling transduction and synaptic transmission proteins in CSIS-sensitive rats. Protein levels of glutamate-related enzymes such as glutamate dehydrogenase and glutamine synthetase were also increased. CSIS-resilient rats showed similar proteome changes, however with a weaker increase compared to CSIS-sensitive rats. The main difference was observed in the level of protein expression of vesicle-mediated transport proteins. Nonetheless, only few proteins were uniquely up-regulated in the CSIS-resilient rats, whereby Cytochrome b-c1 complex subunit 2, mitochondrial (Uqcrc2) and Voltage-dependent anion-selective channel protein 1 (Vdac1) were uniquely down-regulated. Identified altered activated pathways and potential protein biomarkers may help us better understand the molecular mechanisms underlying synaptic neurotransmission in MD or resilience, crucial for development of new therapeutics. © 2020 Elsevier Inc.",
journal = "Brain Research Bulletin",
title = "Hippocampal synaptoproteomic changes of susceptibility and resilience of male rats to chronic social isolation",
volume = "166",
pages = "128-141",
doi = "10.1016/j.brainresbull.2020.11.013"
}

Perić, I., Costina, V., Gass, P., Findeisen, P.,& Filipović, D.. (2021). Hippocampal synaptoproteomic changes of susceptibility and resilience of male rats to chronic social isolation. in Brain Research Bulletin, 166, 128-141.
https://doi.org/10.1016/j.brainresbull.2020.11.013

Perić I, Costina V, Gass P, Findeisen P, Filipović D. Hippocampal synaptoproteomic changes of susceptibility and resilience of male rats to chronic social isolation. in Brain Research Bulletin. 2021;166:128-141.
doi:10.1016/j.brainresbull.2020.11.013 .

Perić, Ivana, Costina, Victor, Gass, Peter, Findeisen, Peter, Filipović, Dragana, "Hippocampal synaptoproteomic changes of susceptibility and resilience of male rats to chronic social isolation" in Brain Research Bulletin, 166 (2021):128-141,
https://doi.org/10.1016/j.brainresbull.2020.11.013 . .

TY  - JOUR
AU  - Filipović, Dragana
AU  - Perić, Ivana
AU  - Costina, Victor
AU  - Stanisavljević, Andrijana
AU  - Gass, Peter
AU  - Findeisen, Peter
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9013
AB  - Aims: To examine the differences in the hippocampal proteome profiles of resilience or susceptibility to chronic social isolation (CSIS), animal model of depression, and to identify biomarkers that can distinguish the two. Main methods: Comparative subproteomic approach was used to identify changes in hippocampal cytosol and nonsynaptic mitochondria (NSM) of CSIS-resilient compared to CSIS-sensitive or control rats. The resilient and sensitive phenotypes of CSIS rats were distinguished based on their sucrose preference values. Selected proteins were validated by Western blot or immunofluorescence. Key findings: Predominantly down-regulated processes such as cytosolic cytoskeleton organization, the calcium signaling pathway, ubiquitin proteasome degradation, redox system, malate/aspartate shuttling and glutamate metabolism in CSIS-resilient compared to CSIS-sensitive rats were found. Decreased protein expression of glycolytic enzymes with simultaneous increased expression of Aco2 involved in tricarboxylic acid cycle and expression of several subunits composing oxidative phosphorylation involved enzymes (Uqcrc2, Atp5f1a, Atp5f1b) were found, indicating shift in energy production from glycolysis to oxidative phosphorylation in NSM. The four-fold higher level of mitochondrial glyceraldehyde-3-phosphate dehydrogenase of resilient rats indicated its transfer from the cytosol to the NSM. An increased level of transketolase along with the reduced pyruvate kinase level suggested an activated pentose phosphate pathway in CSIS-resilient relative to control rats. Cytosolic up-regulated CSIS proteins were implicated in antioxidative and proteasomal systems, while down-regulated NSM protein was involved in oxidative phosphorylation. Significance: The identified altered activated pathways and potential biomarkers enhance understanding of molecular mechanisms underlying resilience or susceptibility to CSIS, crucial in developing new therapeutic strategies.
T2  - Life Sciences
T1  - Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria
VL  - 254
SP  - 117790
DO  - 10.1016/j.lfs.2020.117790
ER  - 

@article{
author = "Filipović, Dragana and Perić, Ivana and Costina, Victor and Stanisavljević, Andrijana and Gass, Peter and Findeisen, Peter",
year = "2020",
abstract = "Aims: To examine the differences in the hippocampal proteome profiles of resilience or susceptibility to chronic social isolation (CSIS), animal model of depression, and to identify biomarkers that can distinguish the two. Main methods: Comparative subproteomic approach was used to identify changes in hippocampal cytosol and nonsynaptic mitochondria (NSM) of CSIS-resilient compared to CSIS-sensitive or control rats. The resilient and sensitive phenotypes of CSIS rats were distinguished based on their sucrose preference values. Selected proteins were validated by Western blot or immunofluorescence. Key findings: Predominantly down-regulated processes such as cytosolic cytoskeleton organization, the calcium signaling pathway, ubiquitin proteasome degradation, redox system, malate/aspartate shuttling and glutamate metabolism in CSIS-resilient compared to CSIS-sensitive rats were found. Decreased protein expression of glycolytic enzymes with simultaneous increased expression of Aco2 involved in tricarboxylic acid cycle and expression of several subunits composing oxidative phosphorylation involved enzymes (Uqcrc2, Atp5f1a, Atp5f1b) were found, indicating shift in energy production from glycolysis to oxidative phosphorylation in NSM. The four-fold higher level of mitochondrial glyceraldehyde-3-phosphate dehydrogenase of resilient rats indicated its transfer from the cytosol to the NSM. An increased level of transketolase along with the reduced pyruvate kinase level suggested an activated pentose phosphate pathway in CSIS-resilient relative to control rats. Cytosolic up-regulated CSIS proteins were implicated in antioxidative and proteasomal systems, while down-regulated NSM protein was involved in oxidative phosphorylation. Significance: The identified altered activated pathways and potential biomarkers enhance understanding of molecular mechanisms underlying resilience or susceptibility to CSIS, crucial in developing new therapeutic strategies.",
journal = "Life Sciences",
title = "Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria",
volume = "254",
pages = "117790",
doi = "10.1016/j.lfs.2020.117790"
}

Filipović, D., Perić, I., Costina, V., Stanisavljević, A., Gass, P.,& Findeisen, P.. (2020). Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria. in Life Sciences, 254, 117790.
https://doi.org/10.1016/j.lfs.2020.117790

Filipović D, Perić I, Costina V, Stanisavljević A, Gass P, Findeisen P. Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria. in Life Sciences. 2020;254:117790.
doi:10.1016/j.lfs.2020.117790 .

Filipović, Dragana, Perić, Ivana, Costina, Victor, Stanisavljević, Andrijana, Gass, Peter, Findeisen, Peter, "Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria" in Life Sciences, 254 (2020):117790,
https://doi.org/10.1016/j.lfs.2020.117790 . .

TY  - JOUR
AU  - Stanisavljević, Andrijana
AU  - Perić, Ivana
AU  - Gass, Peter
AU  - Inta, Dragos
AU  - Lang, Undine E.
AU  - Borgwardt, Stefan
AU  - Filipović, Dragana
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9116
AB  - Antidepressant fluoxetine (Flx) is the first therapeutic choice for the treatment of major depression (MD), however neuroanatomical spots of its action remain unclear. Immunohistochemical detection of c-Fos protein expression has been used for mapping activated neuronal circuits upon various stressors and drugs. We investigated the effect of 3 weeks of Flx treatment (15 mg/kg/day) on changes in neuronal activity, by mapping the number of c-Fos+ cells, in several brain subregions in adult male rats of control and following 3 weeks of chronic social isolation (CSIS), an animal model of depression. The aim was to identify brain subregions activated by vehicle or Flx treatment in both controls or simultaneously applied with CSIS. Flx prevented depressive- and anxiety-like behaviors in CSIS rats. In controls, Flx increased the number of c-Fos+ cells in the anterior/posterior piriform cortex (aPirCx, pPirCx), retrosplenial cortex dysgranular (RSD) and granular, c region (RSGc), dorsal hippocampal subregions (CA1d, CA2, CA3d, DGd), lateral habenula (LHB), paraventricular thalamic nucleus, posterior part (PVP) and lateral/basolateral complex of amygdala (LA/BL). CSIS-induced neuronal activation was observed in brain subregions implicated in mood and other mental disorders such as aPirCx, pPirCx, caudate putamen (CPu), acumbens nucleus shell (AcbSh), RSD, RSGc, DGd, PVP and LA/BL. Flx increased neuronal activation in both controls and CSIS rats in the CA1d, CA2, CA3d, PVP, LA/BL, while in striatum increased neuronal activation was observed only in CSIS. Our data identify activated CSIS-related brain subregions and/or Flx treatment, in which Flx increased c-Fos protein expression in CSIS rats.
T2  - Brain Research Bulletin
T1  - Fluoxetine modulates neuronal activity in stress-related limbic areas of adult rats subjected to the chronic social isolation
VL  - 163
SP  - 95
EP  - 108
DO  - 10.1016/j.brainresbull.2020.07.021
ER  - 

@article{
author = "Stanisavljević, Andrijana and Perić, Ivana and Gass, Peter and Inta, Dragos and Lang, Undine E. and Borgwardt, Stefan and Filipović, Dragana",
year = "2020",
abstract = "Antidepressant fluoxetine (Flx) is the first therapeutic choice for the treatment of major depression (MD), however neuroanatomical spots of its action remain unclear. Immunohistochemical detection of c-Fos protein expression has been used for mapping activated neuronal circuits upon various stressors and drugs. We investigated the effect of 3 weeks of Flx treatment (15 mg/kg/day) on changes in neuronal activity, by mapping the number of c-Fos+ cells, in several brain subregions in adult male rats of control and following 3 weeks of chronic social isolation (CSIS), an animal model of depression. The aim was to identify brain subregions activated by vehicle or Flx treatment in both controls or simultaneously applied with CSIS. Flx prevented depressive- and anxiety-like behaviors in CSIS rats. In controls, Flx increased the number of c-Fos+ cells in the anterior/posterior piriform cortex (aPirCx, pPirCx), retrosplenial cortex dysgranular (RSD) and granular, c region (RSGc), dorsal hippocampal subregions (CA1d, CA2, CA3d, DGd), lateral habenula (LHB), paraventricular thalamic nucleus, posterior part (PVP) and lateral/basolateral complex of amygdala (LA/BL). CSIS-induced neuronal activation was observed in brain subregions implicated in mood and other mental disorders such as aPirCx, pPirCx, caudate putamen (CPu), acumbens nucleus shell (AcbSh), RSD, RSGc, DGd, PVP and LA/BL. Flx increased neuronal activation in both controls and CSIS rats in the CA1d, CA2, CA3d, PVP, LA/BL, while in striatum increased neuronal activation was observed only in CSIS. Our data identify activated CSIS-related brain subregions and/or Flx treatment, in which Flx increased c-Fos protein expression in CSIS rats.",
journal = "Brain Research Bulletin",
title = "Fluoxetine modulates neuronal activity in stress-related limbic areas of adult rats subjected to the chronic social isolation",
volume = "163",
pages = "95-108",
doi = "10.1016/j.brainresbull.2020.07.021"
}

Stanisavljević, A., Perić, I., Gass, P., Inta, D., Lang, U. E., Borgwardt, S.,& Filipović, D.. (2020). Fluoxetine modulates neuronal activity in stress-related limbic areas of adult rats subjected to the chronic social isolation. in Brain Research Bulletin, 163, 95-108.
https://doi.org/10.1016/j.brainresbull.2020.07.021

Stanisavljević A, Perić I, Gass P, Inta D, Lang UE, Borgwardt S, Filipović D. Fluoxetine modulates neuronal activity in stress-related limbic areas of adult rats subjected to the chronic social isolation. in Brain Research Bulletin. 2020;163:95-108.
doi:10.1016/j.brainresbull.2020.07.021 .

Stanisavljević, Andrijana, Perić, Ivana, Gass, Peter, Inta, Dragos, Lang, Undine E., Borgwardt, Stefan, Filipović, Dragana, "Fluoxetine modulates neuronal activity in stress-related limbic areas of adult rats subjected to the chronic social isolation" in Brain Research Bulletin, 163 (2020):95-108,
https://doi.org/10.1016/j.brainresbull.2020.07.021 . .

TY  - JOUR
AU  - Perić, Ivana
AU  - Costina, Victor
AU  - Findeisen, Peter
AU  - Gass, Peter
AU  - Filipović, Dragana
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9721
AB  - Tianeptine (Tian) has been widely used in treating mood and anxiety disorders, and recently as a nootropic to improve cognitive performance. However, its mechanisms of action are insufficiently clear. We used a comparative proteomic approach to identify sub-proteome changes in hippocampal cytosol and non-synaptic mitochondria (NSM) following chronic Tian treatment (3 weeks, 10 mg/kg/day) of adult male Wistar rats and rats exposed to chronic social isolation stress (CSIS) (6 weeks), an animal model of depression. Behavioural assessment of depressive and anxiety-like behaviours was based on sucrose preference, forced swim test and marble burying. Selected differently expressed proteins were validated by Western blot and/or immunohistochemical analysis. Tian normalized the behavioural alternations induced by CSIS, indicating its antidepressant and anxiolytic efficacy. Proteomic data showed that Tian increased the expression of proteasome system elements and redox system enzymes, enhanced energy metabolism and increased glyceraldehyde-3-phosphate dehydrogenase expression bound to NSM in control rats. Tian-treatment of CSIS-stressed rats resulted in a minor suppression of the increase in proteasome elements and antioxidative enzymes, except for an increase in Cu-Zn superoxide dismutase, and increased the level of Lactate dehydrogenase. Our results indicate on an increased NSM functionality in controls and suppression of the CSIS-induced impairment of NSM functionality by Tian treatment as well as on the CSIS-caused discrepancy in Tian effects relative to controls.
T2  - Neuroscience
T1  - Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression
VL  - 451
SP  - 111
EP  - 125
DO  - 10.1016/j.neuroscience.2020.09.061
ER  - 

@article{
author = "Perić, Ivana and Costina, Victor and Findeisen, Peter and Gass, Peter and Filipović, Dragana",
year = "2020",
abstract = "Tianeptine (Tian) has been widely used in treating mood and anxiety disorders, and recently as a nootropic to improve cognitive performance. However, its mechanisms of action are insufficiently clear. We used a comparative proteomic approach to identify sub-proteome changes in hippocampal cytosol and non-synaptic mitochondria (NSM) following chronic Tian treatment (3 weeks, 10 mg/kg/day) of adult male Wistar rats and rats exposed to chronic social isolation stress (CSIS) (6 weeks), an animal model of depression. Behavioural assessment of depressive and anxiety-like behaviours was based on sucrose preference, forced swim test and marble burying. Selected differently expressed proteins were validated by Western blot and/or immunohistochemical analysis. Tian normalized the behavioural alternations induced by CSIS, indicating its antidepressant and anxiolytic efficacy. Proteomic data showed that Tian increased the expression of proteasome system elements and redox system enzymes, enhanced energy metabolism and increased glyceraldehyde-3-phosphate dehydrogenase expression bound to NSM in control rats. Tian-treatment of CSIS-stressed rats resulted in a minor suppression of the increase in proteasome elements and antioxidative enzymes, except for an increase in Cu-Zn superoxide dismutase, and increased the level of Lactate dehydrogenase. Our results indicate on an increased NSM functionality in controls and suppression of the CSIS-induced impairment of NSM functionality by Tian treatment as well as on the CSIS-caused discrepancy in Tian effects relative to controls.",
journal = "Neuroscience",
title = "Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression",
volume = "451",
pages = "111-125",
doi = "10.1016/j.neuroscience.2020.09.061"
}

Perić, I., Costina, V., Findeisen, P., Gass, P.,& Filipović, D.. (2020). Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression. in Neuroscience, 451, 111-125.
https://doi.org/10.1016/j.neuroscience.2020.09.061

Perić I, Costina V, Findeisen P, Gass P, Filipović D. Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression. in Neuroscience. 2020;451:111-125.
doi:10.1016/j.neuroscience.2020.09.061 .

Perić, Ivana, Costina, Victor, Findeisen, Peter, Gass, Peter, Filipović, Dragana, "Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression" in Neuroscience, 451 (2020):111-125,
https://doi.org/10.1016/j.neuroscience.2020.09.061 . .

TY  - JOUR
AU  - Perić, Ivana
AU  - Stanisavljević, Andrijana
AU  - Inta, Dragos
AU  - Gass, Peter
AU  - Undine, Lang E.
AU  - Borgwardt, Stefan
AU  - Filipović, Dragana
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7935
AB  - Adult male rats exposed to chronic social isolation (CSIS) show depressive- and anxiety-like behaviors and reduce the numbers of parvalbumin-positive (PV+) interneurons in the dorsal hippocampus. We aimed to determine whether tianeptine (Tian), administered during the last three weeks of a six-week-social isolation (10 mg/kg/day), may reverse CSIS-induced behavioral changes and antagonize the CSIS-induced reduction in the number of PV+ interneurons. We also studied whether Tian affects the GABA-producing enzyme GAD67+ cells, in Stratum Oriens (SO), Stratum Pyramidale (SP), Stratum Radiatum (SR) and Stratum Lacunosum Moleculare (LM) of CA1-3, as well as in molecular layer-granule cell layer (ML-GCL) and Hilus (H) of the dentate gyrus (DG). CSIS-induced reduction in the number of PV+ cells was layer/subregion-specific with the greatest decrease in SO of CA2. Reduction in the number of PV+ cells was significantly higher than GAD67+ cells, indicating that PV+ cells are the main target following CSIS. Tian reversed CSIS-induced behavior phenotype and antagonized the reduction in the number of PV+ and GAD67+ cells in all subregions. In controls, Tian led to an increase in the number of PV+ and GAD67+ cells in SP of all subregions and PV+ interneurons in ML-GCL of DG, while treatment during CSIS, compared to CSIS alone, resulted with an increase of PV+ interneurons in SO and SP CA1, SP CA2/CA3 and ML-GCL DG with simultaneous increase in GAD67+ cells in all CA1, LM CA2, SO/SR/LM CA3. Data show that Tian offers protection from CSIS via modulation of the dorsal hippocampal GABAergic system.
T2  - Progress in Neuro-Psychopharmacology and Biological Psychiatry
T1  - Tianeptine antagonizes the reduction of PV+ and GAD67 cells number in dorsal hippocampus of socially isolated rats
VL  - 89
SP  - 386
EP  - 399
DO  - 10.1016/j.pnpbp.2018.10.013
ER  - 

@article{
author = "Perić, Ivana and Stanisavljević, Andrijana and Inta, Dragos and Gass, Peter and Undine, Lang E. and Borgwardt, Stefan and Filipović, Dragana",
year = "2019",
abstract = "Adult male rats exposed to chronic social isolation (CSIS) show depressive- and anxiety-like behaviors and reduce the numbers of parvalbumin-positive (PV+) interneurons in the dorsal hippocampus. We aimed to determine whether tianeptine (Tian), administered during the last three weeks of a six-week-social isolation (10 mg/kg/day), may reverse CSIS-induced behavioral changes and antagonize the CSIS-induced reduction in the number of PV+ interneurons. We also studied whether Tian affects the GABA-producing enzyme GAD67+ cells, in Stratum Oriens (SO), Stratum Pyramidale (SP), Stratum Radiatum (SR) and Stratum Lacunosum Moleculare (LM) of CA1-3, as well as in molecular layer-granule cell layer (ML-GCL) and Hilus (H) of the dentate gyrus (DG). CSIS-induced reduction in the number of PV+ cells was layer/subregion-specific with the greatest decrease in SO of CA2. Reduction in the number of PV+ cells was significantly higher than GAD67+ cells, indicating that PV+ cells are the main target following CSIS. Tian reversed CSIS-induced behavior phenotype and antagonized the reduction in the number of PV+ and GAD67+ cells in all subregions. In controls, Tian led to an increase in the number of PV+ and GAD67+ cells in SP of all subregions and PV+ interneurons in ML-GCL of DG, while treatment during CSIS, compared to CSIS alone, resulted with an increase of PV+ interneurons in SO and SP CA1, SP CA2/CA3 and ML-GCL DG with simultaneous increase in GAD67+ cells in all CA1, LM CA2, SO/SR/LM CA3. Data show that Tian offers protection from CSIS via modulation of the dorsal hippocampal GABAergic system.",
journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",
title = "Tianeptine antagonizes the reduction of PV+ and GAD67 cells number in dorsal hippocampus of socially isolated rats",
volume = "89",
pages = "386-399",
doi = "10.1016/j.pnpbp.2018.10.013"
}

Perić, I., Stanisavljević, A., Inta, D., Gass, P., Undine, L. E., Borgwardt, S.,& Filipović, D.. (2019). Tianeptine antagonizes the reduction of PV+ and GAD67 cells number in dorsal hippocampus of socially isolated rats. in Progress in Neuro-Psychopharmacology and Biological Psychiatry, 89, 386-399.
https://doi.org/10.1016/j.pnpbp.2018.10.013

Perić I, Stanisavljević A, Inta D, Gass P, Undine LE, Borgwardt S, Filipović D. Tianeptine antagonizes the reduction of PV+ and GAD67 cells number in dorsal hippocampus of socially isolated rats. in Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2019;89:386-399.
doi:10.1016/j.pnpbp.2018.10.013 .

Perić, Ivana, Stanisavljević, Andrijana, Inta, Dragos, Gass, Peter, Undine, Lang E., Borgwardt, Stefan, Filipović, Dragana, "Tianeptine antagonizes the reduction of PV+ and GAD67 cells number in dorsal hippocampus of socially isolated rats" in Progress in Neuro-Psychopharmacology and Biological Psychiatry, 89 (2019):386-399,
https://doi.org/10.1016/j.pnpbp.2018.10.013 . .

TY  - JOUR
AU  - Stanisavljević, Andrijana
AU  - Perić, Ivana
AU  - Gass, Peter
AU  - Inta, Dragos
AU  - Lang, Undine E.
AU  - Borgwardt, Stefan
AU  - Filipović, Dragana
PY  - 2019
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0306452218307395
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7976
AB  - Olanzapine (Olz) is an atypical antipsychotic used to treat depression, anxiety and schizophrenia, which can be caused by chronic psychosocial stress. c-Fos protein expression has been used as an indirect marker of neuronal activity in response to various forms of stress or pharmacological treatments. We examined the effects of a 3-week treatment of Olz (7.5 mg/kg/day) on c-Fos protein expression in stress-relevant brain sub/regions, its relationship with isolation-induced behavioral changes, and potential sites of Olz action on control and male rats exposed to 6 weeks of chronic social isolation (CSIS), an animal model of depression. Olz treatment reversed depression- and anxiety-like behaviors induced by CSIS and suppressed a CSIS-induced increase in the number of c-Fos-positive cells in subregions of the dorsal hippocampus, ventral (v) DG, retrosplenial cortex, and medial prefrontal cortex. In contrast, no change in c-Fos expression was seen in the CA3v, amygdala and thalamic, hypothalamic or striatal subregions in Olz-treated CSIS rats, suggesting different brain sub/regions’ susceptibility to Olz. An increased number of c-Fos-positive cells in the CA1v, amygdala and thalamic, hypothalamic and striatal subregions in controls as well as in the CA1v and subregion of the hypothalamus and nucleus accumbens in Olz-treated CSIS rats was found. Results suggest the activation of brain sub/regions following CSIS that may be involved in depressive and anxiety-like behaviors. Olz treatment showed region-specific effects on neuronal activation. Our data contribute to a better understanding of the mechanisms underlying the CSIS response and potential brain targets of Olz in socially isolated rats. © 2018 IBRO
T2  - Neuroscience
T1  - Brain Sub/Region-Specific Effects of Olanzapine on c-Fos Expression of Chronically Socially Isolated Rats
VL  - 396
SP  - 46
EP  - 65
DO  - 10.1016/j.neuroscience.2018.11.015
ER  - 

@article{
author = "Stanisavljević, Andrijana and Perić, Ivana and Gass, Peter and Inta, Dragos and Lang, Undine E. and Borgwardt, Stefan and Filipović, Dragana",
year = "2019",
abstract = "Olanzapine (Olz) is an atypical antipsychotic used to treat depression, anxiety and schizophrenia, which can be caused by chronic psychosocial stress. c-Fos protein expression has been used as an indirect marker of neuronal activity in response to various forms of stress or pharmacological treatments. We examined the effects of a 3-week treatment of Olz (7.5 mg/kg/day) on c-Fos protein expression in stress-relevant brain sub/regions, its relationship with isolation-induced behavioral changes, and potential sites of Olz action on control and male rats exposed to 6 weeks of chronic social isolation (CSIS), an animal model of depression. Olz treatment reversed depression- and anxiety-like behaviors induced by CSIS and suppressed a CSIS-induced increase in the number of c-Fos-positive cells in subregions of the dorsal hippocampus, ventral (v) DG, retrosplenial cortex, and medial prefrontal cortex. In contrast, no change in c-Fos expression was seen in the CA3v, amygdala and thalamic, hypothalamic or striatal subregions in Olz-treated CSIS rats, suggesting different brain sub/regions’ susceptibility to Olz. An increased number of c-Fos-positive cells in the CA1v, amygdala and thalamic, hypothalamic and striatal subregions in controls as well as in the CA1v and subregion of the hypothalamus and nucleus accumbens in Olz-treated CSIS rats was found. Results suggest the activation of brain sub/regions following CSIS that may be involved in depressive and anxiety-like behaviors. Olz treatment showed region-specific effects on neuronal activation. Our data contribute to a better understanding of the mechanisms underlying the CSIS response and potential brain targets of Olz in socially isolated rats. © 2018 IBRO",
journal = "Neuroscience",
title = "Brain Sub/Region-Specific Effects of Olanzapine on c-Fos Expression of Chronically Socially Isolated Rats",
volume = "396",
pages = "46-65",
doi = "10.1016/j.neuroscience.2018.11.015"
}

Stanisavljević, A., Perić, I., Gass, P., Inta, D., Lang, U. E., Borgwardt, S.,& Filipović, D.. (2019). Brain Sub/Region-Specific Effects of Olanzapine on c-Fos Expression of Chronically Socially Isolated Rats. in Neuroscience, 396, 46-65.
https://doi.org/10.1016/j.neuroscience.2018.11.015

Stanisavljević A, Perić I, Gass P, Inta D, Lang UE, Borgwardt S, Filipović D. Brain Sub/Region-Specific Effects of Olanzapine on c-Fos Expression of Chronically Socially Isolated Rats. in Neuroscience. 2019;396:46-65.
doi:10.1016/j.neuroscience.2018.11.015 .

Stanisavljević, Andrijana, Perić, Ivana, Gass, Peter, Inta, Dragos, Lang, Undine E., Borgwardt, Stefan, Filipović, Dragana, "Brain Sub/Region-Specific Effects of Olanzapine on c-Fos Expression of Chronically Socially Isolated Rats" in Neuroscience, 396 (2019):46-65,
https://doi.org/10.1016/j.neuroscience.2018.11.015 . .

TY  - JOUR
AU  - Stanisavljević, Andrijana
AU  - Perić, Ivana
AU  - Bernardi, Rick E.
AU  - Gass, Peter
AU  - Filipović, Dragana
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8386
AB  - Chronic social stress and/or pharmacological treatments differentially modulate the expression of c-Fos, a marker of neuronal activity, in subregions of the rat brain. Here, we examined the effect of the atypical antipsychotic Clozapine (Clz) (20 mg/kg/day for 3 weeks) on the neuronal activation pattern of c-Fos protein expression in stress-relevant brain subregions of adult male Wistar rats exposed to chronic social isolation (CSIS: 3 weeks), an animal model of depression and schizophrenia, and controls. The protein expression of c-Fos was also used to map neuronal populations in brain subregions activated by CSIS alone. Subregions which showed significantly increased c-Fos protein expression following CSIS included the retrosplenial cortex (RSC), (subregions:RSC granular cortex, c region (RSGc) and dysgranular (RSD)), dentate gyrus, dorsal (DGd), paraventricular thalamic nucleus, posterior part (PVP), lateral (LA)/basolateral (BL) complex of amygdala, caudate putamen (CPu) and accumbens nucleus, shell (AcbSh). Increases in c-Fos protein expression in the RSGc, RSD, DGd, PVP, LA/BL complex of amygdala and striatum (CPu, Acb Core (AcbC) and AcbSh) following Clz treatment in controls were found. Clz applied simultaneously with CSIS modulated neuronal activity in CPu, AcbC and AcbSh subregions compared to CSIS alone, increasing c-Fos protein expression. Furthermore, Clz revealed synergistic effects with CSIS in the CA1d and PVP. These identified neural circuits reflect brain subregions activated following CSIS and/or Clz administration. These data further contribute to the understanding of the effectiveness of Clz in the modulation of brain subregion activation in response to CSIS. © 2019
T2  - Brain Research Bulletin
T1  - Clozapine increased c-Fos protein expression in several brain subregions of socially isolated rats
VL  - 152
SP  - 35
EP  - 44
DO  - 10.1016/j.brainresbull.2019.07.005
ER  - 

@article{
author = "Stanisavljević, Andrijana and Perić, Ivana and Bernardi, Rick E. and Gass, Peter and Filipović, Dragana",
year = "2019",
abstract = "Chronic social stress and/or pharmacological treatments differentially modulate the expression of c-Fos, a marker of neuronal activity, in subregions of the rat brain. Here, we examined the effect of the atypical antipsychotic Clozapine (Clz) (20 mg/kg/day for 3 weeks) on the neuronal activation pattern of c-Fos protein expression in stress-relevant brain subregions of adult male Wistar rats exposed to chronic social isolation (CSIS: 3 weeks), an animal model of depression and schizophrenia, and controls. The protein expression of c-Fos was also used to map neuronal populations in brain subregions activated by CSIS alone. Subregions which showed significantly increased c-Fos protein expression following CSIS included the retrosplenial cortex (RSC), (subregions:RSC granular cortex, c region (RSGc) and dysgranular (RSD)), dentate gyrus, dorsal (DGd), paraventricular thalamic nucleus, posterior part (PVP), lateral (LA)/basolateral (BL) complex of amygdala, caudate putamen (CPu) and accumbens nucleus, shell (AcbSh). Increases in c-Fos protein expression in the RSGc, RSD, DGd, PVP, LA/BL complex of amygdala and striatum (CPu, Acb Core (AcbC) and AcbSh) following Clz treatment in controls were found. Clz applied simultaneously with CSIS modulated neuronal activity in CPu, AcbC and AcbSh subregions compared to CSIS alone, increasing c-Fos protein expression. Furthermore, Clz revealed synergistic effects with CSIS in the CA1d and PVP. These identified neural circuits reflect brain subregions activated following CSIS and/or Clz administration. These data further contribute to the understanding of the effectiveness of Clz in the modulation of brain subregion activation in response to CSIS. © 2019",
journal = "Brain Research Bulletin",
title = "Clozapine increased c-Fos protein expression in several brain subregions of socially isolated rats",
volume = "152",
pages = "35-44",
doi = "10.1016/j.brainresbull.2019.07.005"
}

Stanisavljević, A., Perić, I., Bernardi, R. E., Gass, P.,& Filipović, D.. (2019). Clozapine increased c-Fos protein expression in several brain subregions of socially isolated rats. in Brain Research Bulletin, 152, 35-44.
https://doi.org/10.1016/j.brainresbull.2019.07.005

Stanisavljević A, Perić I, Bernardi RE, Gass P, Filipović D. Clozapine increased c-Fos protein expression in several brain subregions of socially isolated rats. in Brain Research Bulletin. 2019;152:35-44.
doi:10.1016/j.brainresbull.2019.07.005 .

Stanisavljević, Andrijana, Perić, Ivana, Bernardi, Rick E., Gass, Peter, Filipović, Dragana, "Clozapine increased c-Fos protein expression in several brain subregions of socially isolated rats" in Brain Research Bulletin, 152 (2019):35-44,
https://doi.org/10.1016/j.brainresbull.2019.07.005 . .

TY  - JOUR
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7584
AB  - The dysfunction of parvalbumin-positive (PV+) interneurons, the most abundant type of hippocampal GABAergic inhibitory interneuron, has been implicated in mood disorders. We recently reported that adult male Wistar rats exposed to three weeks of social isolation show depressive-and anxiety-like behaviors and a reduced number of PV+ interneurons in all hippocampal subregions. As GABA neurotransmission has been proposed as a potential therapeutic target of antidepressant and antipsychotic medications, we examined whether treatment with the antidepressant fluoxetine (Flx) (15 mg/kg/day) or the antipsychotic clozapine (Clz) (20 mg/kg/day) during three weeks of social isolation in rats offered protection from the isolation stress-induced reduction in the number of PV+ interneurons in hippocampal subregions. Using immunofluorescence analysis, we revealed that both chronic Flx and Clz partially prevented the isolation-induced changes. Flx prevented the reduction in the number of PV+ interneurons in the CA2, CA3, without affecting the CA1 and dentate gyrus DG areas, whereas Clz prevented this decrement in the CA2, CA3 and DG regions but not in CA1 areas. Moreover, Flx increased the number of PV+ interneurons in CA1 in control animals. These findings suggest that chronic administration of Flx or Clz may offer partial protection from social isolation stress via modulation of the hippocampal GABAergic system. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
T2  - Neuroscience
T1  - Chronic Treatment with Fluoxetine or Clozapine of Socially Isolated Rats Prevents Subsector-Specific Reduction of Parvalbumin Immunoreactive Cells in the Hippocampus
VL  - 371
SP  - 384
EP  - 394
DO  - 10.1016/j.neuroscience.2017.12.020
ER  - 

@article{
year = "2018",
abstract = "The dysfunction of parvalbumin-positive (PV+) interneurons, the most abundant type of hippocampal GABAergic inhibitory interneuron, has been implicated in mood disorders. We recently reported that adult male Wistar rats exposed to three weeks of social isolation show depressive-and anxiety-like behaviors and a reduced number of PV+ interneurons in all hippocampal subregions. As GABA neurotransmission has been proposed as a potential therapeutic target of antidepressant and antipsychotic medications, we examined whether treatment with the antidepressant fluoxetine (Flx) (15 mg/kg/day) or the antipsychotic clozapine (Clz) (20 mg/kg/day) during three weeks of social isolation in rats offered protection from the isolation stress-induced reduction in the number of PV+ interneurons in hippocampal subregions. Using immunofluorescence analysis, we revealed that both chronic Flx and Clz partially prevented the isolation-induced changes. Flx prevented the reduction in the number of PV+ interneurons in the CA2, CA3, without affecting the CA1 and dentate gyrus DG areas, whereas Clz prevented this decrement in the CA2, CA3 and DG regions but not in CA1 areas. Moreover, Flx increased the number of PV+ interneurons in CA1 in control animals. These findings suggest that chronic administration of Flx or Clz may offer partial protection from social isolation stress via modulation of the hippocampal GABAergic system. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.",
journal = "Neuroscience",
title = "Chronic Treatment with Fluoxetine or Clozapine of Socially Isolated Rats Prevents Subsector-Specific Reduction of Parvalbumin Immunoreactive Cells in the Hippocampus",
volume = "371",
pages = "384-394",
doi = "10.1016/j.neuroscience.2017.12.020"
}

(2018). Chronic Treatment with Fluoxetine or Clozapine of Socially Isolated Rats Prevents Subsector-Specific Reduction of Parvalbumin Immunoreactive Cells in the Hippocampus. in Neuroscience, 371, 384-394.
https://doi.org/10.1016/j.neuroscience.2017.12.020

Chronic Treatment with Fluoxetine or Clozapine of Socially Isolated Rats Prevents Subsector-Specific Reduction of Parvalbumin Immunoreactive Cells in the Hippocampus. in Neuroscience. 2018;371:384-394.
doi:10.1016/j.neuroscience.2017.12.020 .

"Chronic Treatment with Fluoxetine or Clozapine of Socially Isolated Rats Prevents Subsector-Specific Reduction of Parvalbumin Immunoreactive Cells in the Hippocampus" in Neuroscience, 371 (2018):384-394,
https://doi.org/10.1016/j.neuroscience.2017.12.020 . .

TY  - JOUR
AU  - Filipović, Dragana
AU  - Todorović, Nevena
AU  - Bernardi, Rick E.
AU  - Gass, Peter
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1392
AB  - Various stressors may disrupt the redox homeostasis of an organism by causing oxidative and nitrosative stress that may activate stressor-specific pathways and provoke specific responses. Chronic social isolation (CSIS) represents a mild chronic stress that evokes a variety of neurobehavioral changes in rats similar to those observed in people with psychiatric disorders, including depression. Most rodent studies have focused on the effect of social isolation during weaning or adolescence, while its effect in adult rats has not been extensively examined. In this review, we discuss the current knowledge regarding the involvement of oxidative/nitrosative stress pathways in the prefrontal cortex and hippocampus of adult male rats exposed to CSIS, focusing on hypothalamic-pituitary-adrenocortical (HPA) axis activity, behavior parameters, antioxidative defense systems, stress signaling mediated by nuclear factor-kappa B (NF-kappa B), and mitochondria-related proapoptotic signaling. Although increased concentrations of corticosterone (CORT) have been shown to induce oxidative and nitrosative stress, we suggest a mechanism underlying the glucocorticoid paradox whereby a state of oxidative/nitrosative stress may exist under basal CORT levels. This review also highlights the differential susceptibility of prefrontal cortex and hippocampus to oxidative stress following CSIS and suggests a possible cellular pathway of stress tolerance that preserves the hippocampus from molecular damage and apoptosis. The differential regulation of the transcriptional factor NF-kappa B, and the enzymes inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) following CSIS may be one functional difference between the response of the prefrontal cortex and hippocampus, thus identifying potentially relevant targets for antidepressant treatment.
T2  - Brain Structure and Function
T1  - Oxidative and nitrosative stress pathways in the brain of socially isolated adult male rats demonstrating depressive- and anxiety-like symptoms
VL  - 222
IS  - 1
SP  - 1
EP  - 20
DO  - 10.1007/s00429-016-1218-9
ER  - 

@article{
author = "Filipović, Dragana and Todorović, Nevena and Bernardi, Rick E. and Gass, Peter",
year = "2017",
abstract = "Various stressors may disrupt the redox homeostasis of an organism by causing oxidative and nitrosative stress that may activate stressor-specific pathways and provoke specific responses. Chronic social isolation (CSIS) represents a mild chronic stress that evokes a variety of neurobehavioral changes in rats similar to those observed in people with psychiatric disorders, including depression. Most rodent studies have focused on the effect of social isolation during weaning or adolescence, while its effect in adult rats has not been extensively examined. In this review, we discuss the current knowledge regarding the involvement of oxidative/nitrosative stress pathways in the prefrontal cortex and hippocampus of adult male rats exposed to CSIS, focusing on hypothalamic-pituitary-adrenocortical (HPA) axis activity, behavior parameters, antioxidative defense systems, stress signaling mediated by nuclear factor-kappa B (NF-kappa B), and mitochondria-related proapoptotic signaling. Although increased concentrations of corticosterone (CORT) have been shown to induce oxidative and nitrosative stress, we suggest a mechanism underlying the glucocorticoid paradox whereby a state of oxidative/nitrosative stress may exist under basal CORT levels. This review also highlights the differential susceptibility of prefrontal cortex and hippocampus to oxidative stress following CSIS and suggests a possible cellular pathway of stress tolerance that preserves the hippocampus from molecular damage and apoptosis. The differential regulation of the transcriptional factor NF-kappa B, and the enzymes inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) following CSIS may be one functional difference between the response of the prefrontal cortex and hippocampus, thus identifying potentially relevant targets for antidepressant treatment.",
journal = "Brain Structure and Function",
title = "Oxidative and nitrosative stress pathways in the brain of socially isolated adult male rats demonstrating depressive- and anxiety-like symptoms",
volume = "222",
number = "1",
pages = "1-20",
doi = "10.1007/s00429-016-1218-9"
}

Filipović, D., Todorović, N., Bernardi, R. E.,& Gass, P.. (2017). Oxidative and nitrosative stress pathways in the brain of socially isolated adult male rats demonstrating depressive- and anxiety-like symptoms. in Brain Structure and Function, 222(1), 1-20.
https://doi.org/10.1007/s00429-016-1218-9

Filipović D, Todorović N, Bernardi RE, Gass P. Oxidative and nitrosative stress pathways in the brain of socially isolated adult male rats demonstrating depressive- and anxiety-like symptoms. in Brain Structure and Function. 2017;222(1):1-20.
doi:10.1007/s00429-016-1218-9 .

Filipović, Dragana, Todorović, Nevena, Bernardi, Rick E., Gass, Peter, "Oxidative and nitrosative stress pathways in the brain of socially isolated adult male rats demonstrating depressive- and anxiety-like symptoms" in Brain Structure and Function, 222, no. 1 (2017):1-20,
https://doi.org/10.1007/s00429-016-1218-9 . .

TY  - JOUR
AU  - Perić, Ivana
AU  - Stanisavljević, Andrijana
AU  - Gass, Peter
AU  - Filipović, Dragana
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1806
AB  - Exposure of an organism to chronic social isolation (CSIS) has been shown to have an important role in depression. Fluoxetine (Flx) is a first-line treatment for depression; however, its downstream mechanisms of action beyond serotonergic signaling remain ill-defined. We investigated the effect of 3 weeks of Flx (15 mg/kg/day) treatment on behavioral changes and protein expression/activity of the GSH-dependent defense system, including reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GLR), and glutathione S-transferase (GST), as well as catalase (CAT), in the hippocampus of rats exposed to 6 weeks of CSIS. The subcellular distributions of nuclear factor-kappa B (NF-kappa B), as well as, cytosolic IL-1 beta and IL-6 protein expression, were also determined. CSIS induced depressive- and anxiety-like behaviors, evidenced by a decrease in sucrose preference and an increase in the number of buried marbles. Moreover, CSIS compromised redox homeostasis, targeting enzymes such as GPx, CAT, GST, and caused NF-kappa B nuclear translocation with a concomitant increase in IL-6 protein expression, without an effect on IL-1 beta. Flx treatment reversed CSIS-induced depressive- and anxiety-like behaviors, modulated GSH-dependent defense by increasing GLR and GST activity, and suppressed NF-kappa B activation and cytosolic IL-6 protein expression in socially isolated rats. The present study suggests that changes in the GSH-dependent defense system, NF-kappa B activation and increased IL-6 protein expression may have a role in social isolation-induced changes in a rat model of depression and anxiety, and contributes to our understanding of the mechanisms that underlie the antidepressant and anti-inflammatory activity of Flx in socially isolated rats.
T2  - European Archives of Psychiatry and Clinical Neuroscience
T1  - Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines
VL  - 267
IS  - 8
SP  - 737
EP  - 749
DO  - 10.1007/s00406-017-0807-9
ER  - 

@article{
author = "Perić, Ivana and Stanisavljević, Andrijana and Gass, Peter and Filipović, Dragana",
year = "2017",
abstract = "Exposure of an organism to chronic social isolation (CSIS) has been shown to have an important role in depression. Fluoxetine (Flx) is a first-line treatment for depression; however, its downstream mechanisms of action beyond serotonergic signaling remain ill-defined. We investigated the effect of 3 weeks of Flx (15 mg/kg/day) treatment on behavioral changes and protein expression/activity of the GSH-dependent defense system, including reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GLR), and glutathione S-transferase (GST), as well as catalase (CAT), in the hippocampus of rats exposed to 6 weeks of CSIS. The subcellular distributions of nuclear factor-kappa B (NF-kappa B), as well as, cytosolic IL-1 beta and IL-6 protein expression, were also determined. CSIS induced depressive- and anxiety-like behaviors, evidenced by a decrease in sucrose preference and an increase in the number of buried marbles. Moreover, CSIS compromised redox homeostasis, targeting enzymes such as GPx, CAT, GST, and caused NF-kappa B nuclear translocation with a concomitant increase in IL-6 protein expression, without an effect on IL-1 beta. Flx treatment reversed CSIS-induced depressive- and anxiety-like behaviors, modulated GSH-dependent defense by increasing GLR and GST activity, and suppressed NF-kappa B activation and cytosolic IL-6 protein expression in socially isolated rats. The present study suggests that changes in the GSH-dependent defense system, NF-kappa B activation and increased IL-6 protein expression may have a role in social isolation-induced changes in a rat model of depression and anxiety, and contributes to our understanding of the mechanisms that underlie the antidepressant and anti-inflammatory activity of Flx in socially isolated rats.",
journal = "European Archives of Psychiatry and Clinical Neuroscience",
title = "Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines",
volume = "267",
number = "8",
pages = "737-749",
doi = "10.1007/s00406-017-0807-9"
}

Perić, I., Stanisavljević, A., Gass, P.,& Filipović, D.. (2017). Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines. in European Archives of Psychiatry and Clinical Neuroscience, 267(8), 737-749.
https://doi.org/10.1007/s00406-017-0807-9

Perić I, Stanisavljević A, Gass P, Filipović D. Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines. in European Archives of Psychiatry and Clinical Neuroscience. 2017;267(8):737-749.
doi:10.1007/s00406-017-0807-9 .

Perić, Ivana, Stanisavljević, Andrijana, Gass, Peter, Filipović, Dragana, "Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines" in European Archives of Psychiatry and Clinical Neuroscience, 267, no. 8 (2017):737-749,
https://doi.org/10.1007/s00406-017-0807-9 . .

TY  - JOUR
AU  - Todorović, Nevena
AU  - Tomanović, Nada
AU  - Gass, Peter
AU  - Filipović, Dragana
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/883
AB  - Olanzapine, an atypical antipsychotic, is efficient in stress associated psychiatric diseases, but its effect on the liver, a primary organ for drug activation and detoxification, still remains unclear. The effect of olanzapine administration (7.5 mg/kg/day), on rat hepatic glutathione (GSH)-dependent defense and proinflammatory cytokines following 6 weeks of chronic social isolation (CSIS), which causes depressive-and anxiety-like behavior in adult male Wistar rats, was investigated. The subcellular distribution of nuclear factor-kappa B (NF-kappa B), cytosolic inducible nitric oxide synthase (iNOS) protein levels and hepatic histological alterations were also determined. Decreased GSH content and glutathione reductase activity associated with increased catalase and glutathione S-transferase activity following CSIS indicated hepatic oxidative stress. Moreover, CSIS caused NF-kappa B nuclear translocation and the concomitant increase in iNOS together with increase in interleukin-1beta and tumor necrosis factor alpha protein levels, but no effect on interleukin-6. Olanzapine treatment suppressed NF-kappa B activation and iNOS expression and caused modulation of GSH-dependent defense systems but failed to reverse CSIS-induced increase in hepatic proinflammatory cytokines. Portal inflammation, focal hepatocyte necrosis and an increased number of Kupffer cells in CSIS rats (vehicle-or olanzapine-treated) were found. Olanzapine-treated socially reared rats showed portal inflammation and focal hepatocyte necrosis. Data suggest that CSIS compromised GSH-dependent defense, triggered a proinflammatory response and histological alterations in rat liver. Olanzapine treatment partially reversed the alterations in hepatic GSH-dependent defense, but showed no anti-inflammatory effect suggesting that it may provide protective effect against hepatic CSIS-induced oxidative stress, but not against inflammation. (C) 2015 Elsevier B.V. All rights reserved.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats
VL  - 81
SP  - 94
EP  - 102
DO  - 10.1016/j.ejps.2015.10.010
ER  - 

@article{
author = "Todorović, Nevena and Tomanović, Nada and Gass, Peter and Filipović, Dragana",
year = "2016",
abstract = "Olanzapine, an atypical antipsychotic, is efficient in stress associated psychiatric diseases, but its effect on the liver, a primary organ for drug activation and detoxification, still remains unclear. The effect of olanzapine administration (7.5 mg/kg/day), on rat hepatic glutathione (GSH)-dependent defense and proinflammatory cytokines following 6 weeks of chronic social isolation (CSIS), which causes depressive-and anxiety-like behavior in adult male Wistar rats, was investigated. The subcellular distribution of nuclear factor-kappa B (NF-kappa B), cytosolic inducible nitric oxide synthase (iNOS) protein levels and hepatic histological alterations were also determined. Decreased GSH content and glutathione reductase activity associated with increased catalase and glutathione S-transferase activity following CSIS indicated hepatic oxidative stress. Moreover, CSIS caused NF-kappa B nuclear translocation and the concomitant increase in iNOS together with increase in interleukin-1beta and tumor necrosis factor alpha protein levels, but no effect on interleukin-6. Olanzapine treatment suppressed NF-kappa B activation and iNOS expression and caused modulation of GSH-dependent defense systems but failed to reverse CSIS-induced increase in hepatic proinflammatory cytokines. Portal inflammation, focal hepatocyte necrosis and an increased number of Kupffer cells in CSIS rats (vehicle-or olanzapine-treated) were found. Olanzapine-treated socially reared rats showed portal inflammation and focal hepatocyte necrosis. Data suggest that CSIS compromised GSH-dependent defense, triggered a proinflammatory response and histological alterations in rat liver. Olanzapine treatment partially reversed the alterations in hepatic GSH-dependent defense, but showed no anti-inflammatory effect suggesting that it may provide protective effect against hepatic CSIS-induced oxidative stress, but not against inflammation. (C) 2015 Elsevier B.V. All rights reserved.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats",
volume = "81",
pages = "94-102",
doi = "10.1016/j.ejps.2015.10.010"
}

Todorović, N., Tomanović, N., Gass, P.,& Filipović, D.. (2016). Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats. in European Journal of Pharmaceutical Sciences
Elsevier., 81, 94-102.
https://doi.org/10.1016/j.ejps.2015.10.010

Todorović N, Tomanović N, Gass P, Filipović D. Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats. in European Journal of Pharmaceutical Sciences. 2016;81:94-102.
doi:10.1016/j.ejps.2015.10.010 .

Todorović, Nevena, Tomanović, Nada, Gass, Peter, Filipović, Dragana, "Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats" in European Journal of Pharmaceutical Sciences, 81 (2016):94-102,
https://doi.org/10.1016/j.ejps.2015.10.010 . .

TY  - JOUR
AU  - Filipović, Dragana
AU  - Martinović, Jelena
AU  - Gass, Peter
AU  - Inta, Dragos
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5391
AB  - The hippocampus plays a central role in stress-related mood disorders. The effects of acute vs. chronic stress on the integrity of hippocampal circuitry in influencing the vulnerability to, or resiliency against, neuronal injury are poorly understood. Here we investigated whether acute vs. chronic psychosocial isolation stress or a combination of the two (chronic stress followed by acute stress) influences the expression of the interneuronal marker parvalbumin (PV) and the chaperone-inducible heat shock protein 70 (Hsp70i) in different subregions of the hippocampus. Low levels of the Ca2+-binding protein (PV) may increase the vulnerability to neuronal injury, and Hsp70i represents an indicator of intense excitation-induced neuronal stress. Adult male Wistar rats were exposed to 2 h of immobilization (IM) or cold (4 degrees C) (acute stressors), 21 d of social isolation (chronic stress), or a combination of both acute and chronic stress. Both chronic isolation and the combined stressors strongly decreased the PV-Immunoreactive cells in the CA1, CA3 and dentate gyrus (DG) region of the hippocampus, while acute stress did not affect PV expression. The combination of acute and chronic stress induced a dramatic increase in Hsp70i expression in the DG, but Hsp70i expression was unaffected in acute and chronic stress alone. We also monitored serum corticosterone (CORT) levels as a neuroendocrine marker of the stress response. Acute stress increased CORT levels, while chronic isolation stress compromised hypothalamic pituitary adrenocortical (HPA) axis activity such that the normal stress response was impaired following subsequent acute stress. These results indicate that in contrast to acute stress, chronic isolation compromises the HPA axis and generates a considerable reduction in PV expression, representing a decrease in the calcium-buffering capacity and a putatively higher vulnerability of specific hippocampal interneurons to excitotoxic injury. The induction of Hsp70i expression in response to acute and chronic isolation reveals that neurons in the DG are particularly vulnerable to an acute stressor following a chronic perturbation of HPA activity. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
T2  - Neuroscience
T1  - The Differential Effects of Acute Vs. Chronic Stress and Their Combination on Hippocampal Parvalbumin and Inducible Heat Shock Protein 70 Expression
VL  - 236
SP  - 47
EP  - 54
DO  - 10.1016/j.neuroscience.2013.01.033
ER  - 

@article{
author = "Filipović, Dragana and Martinović, Jelena and Gass, Peter and Inta, Dragos",
year = "2013",
abstract = "The hippocampus plays a central role in stress-related mood disorders. The effects of acute vs. chronic stress on the integrity of hippocampal circuitry in influencing the vulnerability to, or resiliency against, neuronal injury are poorly understood. Here we investigated whether acute vs. chronic psychosocial isolation stress or a combination of the two (chronic stress followed by acute stress) influences the expression of the interneuronal marker parvalbumin (PV) and the chaperone-inducible heat shock protein 70 (Hsp70i) in different subregions of the hippocampus. Low levels of the Ca2+-binding protein (PV) may increase the vulnerability to neuronal injury, and Hsp70i represents an indicator of intense excitation-induced neuronal stress. Adult male Wistar rats were exposed to 2 h of immobilization (IM) or cold (4 degrees C) (acute stressors), 21 d of social isolation (chronic stress), or a combination of both acute and chronic stress. Both chronic isolation and the combined stressors strongly decreased the PV-Immunoreactive cells in the CA1, CA3 and dentate gyrus (DG) region of the hippocampus, while acute stress did not affect PV expression. The combination of acute and chronic stress induced a dramatic increase in Hsp70i expression in the DG, but Hsp70i expression was unaffected in acute and chronic stress alone. We also monitored serum corticosterone (CORT) levels as a neuroendocrine marker of the stress response. Acute stress increased CORT levels, while chronic isolation stress compromised hypothalamic pituitary adrenocortical (HPA) axis activity such that the normal stress response was impaired following subsequent acute stress. These results indicate that in contrast to acute stress, chronic isolation compromises the HPA axis and generates a considerable reduction in PV expression, representing a decrease in the calcium-buffering capacity and a putatively higher vulnerability of specific hippocampal interneurons to excitotoxic injury. The induction of Hsp70i expression in response to acute and chronic isolation reveals that neurons in the DG are particularly vulnerable to an acute stressor following a chronic perturbation of HPA activity. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.",
journal = "Neuroscience",
title = "The Differential Effects of Acute Vs. Chronic Stress and Their Combination on Hippocampal Parvalbumin and Inducible Heat Shock Protein 70 Expression",
volume = "236",
pages = "47-54",
doi = "10.1016/j.neuroscience.2013.01.033"
}

Filipović, D., Martinović, J., Gass, P.,& Inta, D.. (2013). The Differential Effects of Acute Vs. Chronic Stress and Their Combination on Hippocampal Parvalbumin and Inducible Heat Shock Protein 70 Expression. in Neuroscience, 236, 47-54.
https://doi.org/10.1016/j.neuroscience.2013.01.033

Filipović D, Martinović J, Gass P, Inta D. The Differential Effects of Acute Vs. Chronic Stress and Their Combination on Hippocampal Parvalbumin and Inducible Heat Shock Protein 70 Expression. in Neuroscience. 2013;236:47-54.
doi:10.1016/j.neuroscience.2013.01.033 .

Filipović, Dragana, Martinović, Jelena, Gass, Peter, Inta, Dragos, "The Differential Effects of Acute Vs. Chronic Stress and Their Combination on Hippocampal Parvalbumin and Inducible Heat Shock Protein 70 Expression" in Neuroscience, 236 (2013):47-54,
https://doi.org/10.1016/j.neuroscience.2013.01.033 . .

TY  - JOUR
AU  - Inta, Dragos
AU  - Vogt, M. A.
AU  - Luoni, A.
AU  - Filipović, Dragana
AU  - Lima-Ojeda, J. M.
AU  - Pfeiffer, N.
AU  - Gasparini, F.
AU  - Riva, M. A.
AU  - Gass, Peter
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5328
AB  - Glutamatergic mechanisms regulate neuronal circuits implicated in mood and anxiety. Emotional disorders as anxiety and depression are particularly difficult to treat during aging and mechanisms underlying emotional disturbances in the brain of the elderly are poorly understood. This may result from the small number of studies investigating these disorders in aged animals. Among glutamate receptors, metabotropic mGlu5 receptors are thought to play an important role, since their pharmacological blockade induces strong anxiolytic effects. However, the implication of mGlu5 in regulating anxiety is not yet completely understood. Here we analyzed both young adult and aged mice lacking mGlu5 receptors, to clarify, if genetic deletion of the receptor induces similar to pharmacological blockade anxiolytic effects. Unexpectedly, mGlu5 receptor knockout (KO) mice showed increased anxiety accentuating with aging. In contrast, young adult mice displayed an anti-depressive-like phenotype that was no longer detectable in aged animals. Our data support important distinct roles of mGlu5 receptors in modulating anxiety and depression during aging. (C) 2012 Elsevier B.V. All rights reserved.
T2  - Behavioural Brain Research
T1  - Significant increase in anxiety during aging in mGlu5 receptor knockout mice
VL  - 241
SP  - 27
EP  - 31
DO  - 10.1016/j.bbr.2012.11.042
ER  - 

@article{
author = "Inta, Dragos and Vogt, M. A. and Luoni, A. and Filipović, Dragana and Lima-Ojeda, J. M. and Pfeiffer, N. and Gasparini, F. and Riva, M. A. and Gass, Peter",
year = "2013",
abstract = "Glutamatergic mechanisms regulate neuronal circuits implicated in mood and anxiety. Emotional disorders as anxiety and depression are particularly difficult to treat during aging and mechanisms underlying emotional disturbances in the brain of the elderly are poorly understood. This may result from the small number of studies investigating these disorders in aged animals. Among glutamate receptors, metabotropic mGlu5 receptors are thought to play an important role, since their pharmacological blockade induces strong anxiolytic effects. However, the implication of mGlu5 in regulating anxiety is not yet completely understood. Here we analyzed both young adult and aged mice lacking mGlu5 receptors, to clarify, if genetic deletion of the receptor induces similar to pharmacological blockade anxiolytic effects. Unexpectedly, mGlu5 receptor knockout (KO) mice showed increased anxiety accentuating with aging. In contrast, young adult mice displayed an anti-depressive-like phenotype that was no longer detectable in aged animals. Our data support important distinct roles of mGlu5 receptors in modulating anxiety and depression during aging. (C) 2012 Elsevier B.V. All rights reserved.",
journal = "Behavioural Brain Research",
title = "Significant increase in anxiety during aging in mGlu5 receptor knockout mice",
volume = "241",
pages = "27-31",
doi = "10.1016/j.bbr.2012.11.042"
}

Inta, D., Vogt, M. A., Luoni, A., Filipović, D., Lima-Ojeda, J. M., Pfeiffer, N., Gasparini, F., Riva, M. A.,& Gass, P.. (2013). Significant increase in anxiety during aging in mGlu5 receptor knockout mice. in Behavioural Brain Research, 241, 27-31.
https://doi.org/10.1016/j.bbr.2012.11.042

Inta D, Vogt MA, Luoni A, Filipović D, Lima-Ojeda JM, Pfeiffer N, Gasparini F, Riva MA, Gass P. Significant increase in anxiety during aging in mGlu5 receptor knockout mice. in Behavioural Brain Research. 2013;241:27-31.
doi:10.1016/j.bbr.2012.11.042 .

Inta, Dragos, Vogt, M. A., Luoni, A., Filipović, Dragana, Lima-Ojeda, J. M., Pfeiffer, N., Gasparini, F., Riva, M. A., Gass, Peter, "Significant increase in anxiety during aging in mGlu5 receptor knockout mice" in Behavioural Brain Research, 241 (2013):27-31,
https://doi.org/10.1016/j.bbr.2012.11.042 . .

TY  - JOUR
AU  - Inta, Dragos
AU  - Filipović, Dragana
AU  - Lima-Ojeda, Juan M.
AU  - Dormann, Christof
AU  - Pfeiffer, Natascha
AU  - Gasparini, Fabrizio
AU  - Gass, Peter
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4741
AB  - Glutamatergic agents have been conceptualized as powerful, fast-acting alternatives to monoaminergic-based antidepressants. NMDA receptor antagonists such as ketamine or MK-801 are therapeutically effective, but their clinical use is hampered by psychotomimetic effects, accompanied by neurotoxicity in the retrosplenial and cingulate cortex. Antagonists of metabotropic mGlu5 receptors like MPEP elicit both robust antidepressant and anxiolytic effects; however, the underlying mechanisms are yet unknown. mGlu5 receptors closely interact with NMDA receptors, but whether MPEP induces neurotoxicity similar to NMDA receptor antagonists has not been elucidated. We show here using c-Fos brain mapping that MPEP administration results in a restricted activation of distinct stress-related brain areas, including the bed nucleus of stria terminalis (BNST), central nucleus of the amygdala, and paraventricular nucleus of the hypothalamus (PVNH), in a pattern similar to that induced by classical antidepressants and anxio-lytics. Unlike the NMDA antagonist MK-801, MPEP does not injure the adult retrosplenial cortex, in which it fails to induce heat shock protein 70 (Hsp70). Moreover, MPEP does not elicit to the same extent as MK-801 apoptosis in cortical areas at perinatal stages, as revealed by caspase 3 expression. These data identify new cellular targets for the anxiolytic and antidepressant effect of MPEP, indicating also in addition that in contrast to MK-801, it lacks the cortical neurotoxicity associated with psychotomimetic side-effects. (C) 2012 Elsevier Ltd. All rights reserved.
T2  - Neuropharmacology
T1  - The mGlu5 receptor antagonist MPEP activates specific stress-related brain regions and lacks neurotoxic effects of the NMDA receptor antagonist MK-801: Significance for the use as anxiolytic/antidepressant drug
VL  - 62
IS  - 5-6
SP  - 2034
EP  - 2039
DO  - 10.1016/j.neuropharm.2011.12.035
ER  - 

@article{
author = "Inta, Dragos and Filipović, Dragana and Lima-Ojeda, Juan M. and Dormann, Christof and Pfeiffer, Natascha and Gasparini, Fabrizio and Gass, Peter",
year = "2012",
abstract = "Glutamatergic agents have been conceptualized as powerful, fast-acting alternatives to monoaminergic-based antidepressants. NMDA receptor antagonists such as ketamine or MK-801 are therapeutically effective, but their clinical use is hampered by psychotomimetic effects, accompanied by neurotoxicity in the retrosplenial and cingulate cortex. Antagonists of metabotropic mGlu5 receptors like MPEP elicit both robust antidepressant and anxiolytic effects; however, the underlying mechanisms are yet unknown. mGlu5 receptors closely interact with NMDA receptors, but whether MPEP induces neurotoxicity similar to NMDA receptor antagonists has not been elucidated. We show here using c-Fos brain mapping that MPEP administration results in a restricted activation of distinct stress-related brain areas, including the bed nucleus of stria terminalis (BNST), central nucleus of the amygdala, and paraventricular nucleus of the hypothalamus (PVNH), in a pattern similar to that induced by classical antidepressants and anxio-lytics. Unlike the NMDA antagonist MK-801, MPEP does not injure the adult retrosplenial cortex, in which it fails to induce heat shock protein 70 (Hsp70). Moreover, MPEP does not elicit to the same extent as MK-801 apoptosis in cortical areas at perinatal stages, as revealed by caspase 3 expression. These data identify new cellular targets for the anxiolytic and antidepressant effect of MPEP, indicating also in addition that in contrast to MK-801, it lacks the cortical neurotoxicity associated with psychotomimetic side-effects. (C) 2012 Elsevier Ltd. All rights reserved.",
journal = "Neuropharmacology",
title = "The mGlu5 receptor antagonist MPEP activates specific stress-related brain regions and lacks neurotoxic effects of the NMDA receptor antagonist MK-801: Significance for the use as anxiolytic/antidepressant drug",
volume = "62",
number = "5-6",
pages = "2034-2039",
doi = "10.1016/j.neuropharm.2011.12.035"
}

Inta, D., Filipović, D., Lima-Ojeda, J. M., Dormann, C., Pfeiffer, N., Gasparini, F.,& Gass, P.. (2012). The mGlu5 receptor antagonist MPEP activates specific stress-related brain regions and lacks neurotoxic effects of the NMDA receptor antagonist MK-801: Significance for the use as anxiolytic/antidepressant drug. in Neuropharmacology, 62(5-6), 2034-2039.
https://doi.org/10.1016/j.neuropharm.2011.12.035

Inta D, Filipović D, Lima-Ojeda JM, Dormann C, Pfeiffer N, Gasparini F, Gass P. The mGlu5 receptor antagonist MPEP activates specific stress-related brain regions and lacks neurotoxic effects of the NMDA receptor antagonist MK-801: Significance for the use as anxiolytic/antidepressant drug. in Neuropharmacology. 2012;62(5-6):2034-2039.
doi:10.1016/j.neuropharm.2011.12.035 .

Inta, Dragos, Filipović, Dragana, Lima-Ojeda, Juan M., Dormann, Christof, Pfeiffer, Natascha, Gasparini, Fabrizio, Gass, Peter, "The mGlu5 receptor antagonist MPEP activates specific stress-related brain regions and lacks neurotoxic effects of the NMDA receptor antagonist MK-801: Significance for the use as anxiolytic/antidepressant drug" in Neuropharmacology, 62, no. 5-6 (2012):2034-2039,
https://doi.org/10.1016/j.neuropharm.2011.12.035 . .

TY  - JOUR
AU  - Filipović, Dragana
AU  - Martinović, Jelena
AU  - Inta, Dragos
AU  - Bjelobaba, I.
AU  - Stojiljković, Mirjana
AU  - Gass, Peter
PY  - 2011
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4409
AB  - Mitochondria are central integrators and transducers of proapoptotic signals for neuronal apoptosis. The tumor suppressor protein p53 can trigger apoptosis independently of its transcriptional activity, through subcellular translocation of cytochrome c and caspase activation. To define better the proapoptotic role of p53 under various stress conditions, we investigated the protein levels of p53 and cytochrome c in mitochondrial and cytosolic fractions, as well as caspase-3 activation and apoptosis, in the prefrontal cortex and hippocampus of male Wistar rats subjected to acute, chronic, or combined stressors. Mitochondrial p53 can suppress the antioxidant enzyme MnSOD, so its activity was also determined. In the prefrontal cortex, but not in hippocampus, increased protein levels of p53 were found in mitochondria, leading to cytochrome c release into cytoplasm, activation of caspase-3, and apoptotic cell death following combined stressors. Decreased mitochondrial MnSOD activity following combined stressors in both brain structures indicated a state of oxidative stress. This suggests that chronic isolation stress compromises mitochondrial MnSOD activity in both the prefrontal cortex and the hippocampus but likely results in mitochondrial-triggered proapoptotic signaling mediated by a transcription-independent p53 mechanism only in the prefrontal cortex. Thus, our data demonstrate a tissue-specific (prefrontal cortex vs. hippocampus) response to applied stressors. (C) 2011 Wiley-Liss, Inc.
T2  - Journal of Neuroscience Research
T1  - Chronic Isolation Stress Predisposes the Frontal Cortex but Not the Hippocampus to the Potentially Detrimental Release of Cytochrome c From Mitochondria and the Activation of Caspase-3
VL  - 89
IS  - 9
SP  - 1461
EP  - 1470
DO  - 10.1002/jnr.22687
ER  - 

@article{
author = "Filipović, Dragana and Martinović, Jelena and Inta, Dragos and Bjelobaba, I. and Stojiljković, Mirjana and Gass, Peter",
year = "2011",
abstract = "Mitochondria are central integrators and transducers of proapoptotic signals for neuronal apoptosis. The tumor suppressor protein p53 can trigger apoptosis independently of its transcriptional activity, through subcellular translocation of cytochrome c and caspase activation. To define better the proapoptotic role of p53 under various stress conditions, we investigated the protein levels of p53 and cytochrome c in mitochondrial and cytosolic fractions, as well as caspase-3 activation and apoptosis, in the prefrontal cortex and hippocampus of male Wistar rats subjected to acute, chronic, or combined stressors. Mitochondrial p53 can suppress the antioxidant enzyme MnSOD, so its activity was also determined. In the prefrontal cortex, but not in hippocampus, increased protein levels of p53 were found in mitochondria, leading to cytochrome c release into cytoplasm, activation of caspase-3, and apoptotic cell death following combined stressors. Decreased mitochondrial MnSOD activity following combined stressors in both brain structures indicated a state of oxidative stress. This suggests that chronic isolation stress compromises mitochondrial MnSOD activity in both the prefrontal cortex and the hippocampus but likely results in mitochondrial-triggered proapoptotic signaling mediated by a transcription-independent p53 mechanism only in the prefrontal cortex. Thus, our data demonstrate a tissue-specific (prefrontal cortex vs. hippocampus) response to applied stressors. (C) 2011 Wiley-Liss, Inc.",
journal = "Journal of Neuroscience Research",
title = "Chronic Isolation Stress Predisposes the Frontal Cortex but Not the Hippocampus to the Potentially Detrimental Release of Cytochrome c From Mitochondria and the Activation of Caspase-3",
volume = "89",
number = "9",
pages = "1461-1470",
doi = "10.1002/jnr.22687"
}

Filipović, D., Martinović, J., Inta, D., Bjelobaba, I., Stojiljković, M.,& Gass, P.. (2011). Chronic Isolation Stress Predisposes the Frontal Cortex but Not the Hippocampus to the Potentially Detrimental Release of Cytochrome c From Mitochondria and the Activation of Caspase-3. in Journal of Neuroscience Research, 89(9), 1461-1470.
https://doi.org/10.1002/jnr.22687

Filipović D, Martinović J, Inta D, Bjelobaba I, Stojiljković M, Gass P. Chronic Isolation Stress Predisposes the Frontal Cortex but Not the Hippocampus to the Potentially Detrimental Release of Cytochrome c From Mitochondria and the Activation of Caspase-3. in Journal of Neuroscience Research. 2011;89(9):1461-1470.
doi:10.1002/jnr.22687 .

Filipović, Dragana, Martinović, Jelena, Inta, Dragos, Bjelobaba, I., Stojiljković, Mirjana, Gass, Peter, "Chronic Isolation Stress Predisposes the Frontal Cortex but Not the Hippocampus to the Potentially Detrimental Release of Cytochrome c From Mitochondria and the Activation of Caspase-3" in Journal of Neuroscience Research, 89, no. 9 (2011):1461-1470,
https://doi.org/10.1002/jnr.22687 . .

TY  - CONF
AU  - Inta, Dragos
AU  - Lima, J.
AU  - Filipović, Dragana
AU  - Koehr, G.
AU  - Sprengel, R.
AU  - Gass, Peter
PY  - 2011
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/2731
C3  - European Psychiatry
T1  - C-Fos Brain Mapping of Global and Subunit-Specific Nmda Receptor Antagonists: Relevance for Their Potential Use as Antidepressants
VL  - 26
UR  - https://hdl.handle.net/21.15107/rcub_vinar_2731
ER  - 

@conference{
author = "Inta, Dragos and Lima, J. and Filipović, Dragana and Koehr, G. and Sprengel, R. and Gass, Peter",
year = "2011",
journal = "European Psychiatry",
title = "C-Fos Brain Mapping of Global and Subunit-Specific Nmda Receptor Antagonists: Relevance for Their Potential Use as Antidepressants",
volume = "26",
url = "https://hdl.handle.net/21.15107/rcub_vinar_2731"
}

Inta, D., Lima, J., Filipović, D., Koehr, G., Sprengel, R.,& Gass, P.. (2011). C-Fos Brain Mapping of Global and Subunit-Specific Nmda Receptor Antagonists: Relevance for Their Potential Use as Antidepressants. in European Psychiatry, 26.
https://hdl.handle.net/21.15107/rcub_vinar_2731

Inta D, Lima J, Filipović D, Koehr G, Sprengel R, Gass P. C-Fos Brain Mapping of Global and Subunit-Specific Nmda Receptor Antagonists: Relevance for Their Potential Use as Antidepressants. in European Psychiatry. 2011;26.
https://hdl.handle.net/21.15107/rcub_vinar_2731 .

Inta, Dragos, Lima, J., Filipović, Dragana, Koehr, G., Sprengel, R., Gass, Peter, "C-Fos Brain Mapping of Global and Subunit-Specific Nmda Receptor Antagonists: Relevance for Their Potential Use as Antidepressants" in European Psychiatry, 26 (2011),
https://hdl.handle.net/21.15107/rcub_vinar_2731 .