Filipović, Dragana

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Authority KeyName Variants
orcid::0000-0002-7828-4168
  • Filipović, Dragana (58)
Projects
Molecular mechanisms of cellular responses on pathological changes in central neuronal system and peripheral organs of mammals Effects of metabolic and nonmetabolic stressors on the expression and action of neuroendocrine regulators of energy homeostasis
Signalni putevi delovanja steroidnih hormona i uticaj endogenih i egzogenih faktora na modulaciju procesa u ćelijama sisara Ministry of Education, Science and Technological Development of the Republic of Serbia
Deutsche Forschungsgemeinschaft [SFB636-TP3] Antioxidative defense, differentiation and regeneration potential of tissue specific mesenchymal stem cells during ageing
DAAD, Heidelberg University Deutsche Forschungsgemeinschaf (Forschergruppe 2591 ‘Severity assessment in animal-based research) [P05]
Deutsche Forschungsgemeinschaft [GA427/11-1], DAAD, BASILEUS fellowship, DAAD-CONACYT fellowship Deutsche Forschungsgemeinschaft [GA427/11-1], DAAD-CONACYT, DAAD
Deutsche Forschungsgemeinschaft [GA427/11-1], Heidelberg University, Germany Deutsche Forschungsgemeinschaft [GA 427/12-1]
Deutsche Forschungsgemeinschaft (IN168/3-1) Deutsche Forschungsgemeinschaft [IN168/3-1]
Deutsche Forschungsgemeinschaft [IN168/3-1, SFB636-TP3]; Ingeborg Stander Foundation; Research Fund of the UPK Basel; German Ministry of Education and Research (BMBF) [01GQ1003B] Deutsche Forschungsgemeinschaft [SFB636-TP3], German Ministry of Education and Research (BMBF) [01GQ1003B]
Federal Ministry of Education & Research (BMBF) [01EW1807A] German Research Foundation (DFG) [DI 168/3-1]
German Research Foundation (DFG) [GA 427/12-1] Studying signal transduction pathways and epigenetic mechanisms that control human SOX genes expression: further insight into their roles in cell fate determination and differentiation
Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200017 (University of Belgrade, Institute of Nuclear Sciences 'Vinča', Belgrade-Vinča) Cellular and molecular basis of neuroinflamation: potential targets for translational medicine and therapy
Ingeborg Stander Foundation Ministry of Education, Science and Technological Development of the Republic of Serbia and the Deutsche Forschungsgemeinschaft [DFG, GA 427/12-1]
Slovenian Research Agency, FEBS, Ad Futura Agency of Slovenia Slovenian Research Agency, Federation of European Biochemical Societies, Ad Futura Agency of Slovenia
Swiss National Science Foundation (SNSF) [186346]

Author's Bibliography

Fluoxetine exerts subregion/layer specific effects on parvalbumin/GAD67 protein expression in the dorsal hippocampus of male rats showing social isolation-induced depressive-like behaviour

Perić, Ivana; Stanisavljević, Andrijana; Gass, Peter; Filipović, Dragana

(2021)

TY  - JOUR
AU  - Perić, Ivana
AU  - Stanisavljević, Andrijana
AU  - Gass, Peter
AU  - Filipović, Dragana
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9817
AB  - The molecular background of depression is intensively studied in terms of alterations of inhibitory circuits, mediated by gamma aminobutyric acid (GABA) signalization. We investigated the effects of chronic social isolation (CSIS) and chronic fluoxetine (Flx) treatment (15 mg/kg/day) (3 weeks), on Parvalbumin (PV) and GAD67 expression in a layer-specific manner in rat dorsal hippocampal subregions. CSIS-induced depressive- and anxiety-like behaviours were confirmed with decrease in sucrose preference and increase in marble burying during behavioural testing, while Flx antagonized these effects. CSIS altered PV expression in stratum pyramidale (SP) of dorsal cornu ammonis 1 (dCA1) and stratum radiatum (SR) of dCA3. Flx antagonized this effect, and boosted PV expression in SP of the entire dCA and the dorsal dentate gyrus (dDG), as well as in the SR of dCA1/CA3. CSIS showed no significant effects on GAD67 expression, while Flx boosted its expression within the SR of the entire CA and SO of the dCA3. A correlation between SP of dCA1 and SR of dCA3 with regard to PV changes, implicates their possible role in the inhibitory circuit alterations. Flx-induced increase in GAD67 expression, specifically in SR of the entire dHIPP, may impose its involvement in the cell metabolic processes. Strong negative correlation between GAD67 and sucrose preference following Flx-treatment of CSIS rats was revealed. PV + cells of the SP layer of dCA1 and CA2 could be a potential target for the antidepressant action of Flx, while strong effect of Flx on GAD67 expression in the SR should be more extensively studied.
T2  - Brain Research Bulletin
T1  - Fluoxetine exerts subregion/layer specific effects on parvalbumin/GAD67 protein expression in the dorsal hippocampus of male rats showing social isolation-induced depressive-like behaviour
VL  - 173
SP  - 174
EP  - 183
DO  - 10.1016/j.brainresbull.2021.05.021
ER  - 
@article{
author = "Perić, Ivana and Stanisavljević, Andrijana and Gass, Peter and Filipović, Dragana",
year = "2021",
abstract = "The molecular background of depression is intensively studied in terms of alterations of inhibitory circuits, mediated by gamma aminobutyric acid (GABA) signalization. We investigated the effects of chronic social isolation (CSIS) and chronic fluoxetine (Flx) treatment (15 mg/kg/day) (3 weeks), on Parvalbumin (PV) and GAD67 expression in a layer-specific manner in rat dorsal hippocampal subregions. CSIS-induced depressive- and anxiety-like behaviours were confirmed with decrease in sucrose preference and increase in marble burying during behavioural testing, while Flx antagonized these effects. CSIS altered PV expression in stratum pyramidale (SP) of dorsal cornu ammonis 1 (dCA1) and stratum radiatum (SR) of dCA3. Flx antagonized this effect, and boosted PV expression in SP of the entire dCA and the dorsal dentate gyrus (dDG), as well as in the SR of dCA1/CA3. CSIS showed no significant effects on GAD67 expression, while Flx boosted its expression within the SR of the entire CA and SO of the dCA3. A correlation between SP of dCA1 and SR of dCA3 with regard to PV changes, implicates their possible role in the inhibitory circuit alterations. Flx-induced increase in GAD67 expression, specifically in SR of the entire dHIPP, may impose its involvement in the cell metabolic processes. Strong negative correlation between GAD67 and sucrose preference following Flx-treatment of CSIS rats was revealed. PV + cells of the SP layer of dCA1 and CA2 could be a potential target for the antidepressant action of Flx, while strong effect of Flx on GAD67 expression in the SR should be more extensively studied.",
journal = "Brain Research Bulletin",
title = "Fluoxetine exerts subregion/layer specific effects on parvalbumin/GAD67 protein expression in the dorsal hippocampus of male rats showing social isolation-induced depressive-like behaviour",
volume = "173",
pages = "174-183",
doi = "10.1016/j.brainresbull.2021.05.021"
}
Perić, I., Stanisavljević, A., Gass, P.,& Filipović, D.. (2021). Fluoxetine exerts subregion/layer specific effects on parvalbumin/GAD67 protein expression in the dorsal hippocampus of male rats showing social isolation-induced depressive-like behaviour. in Brain Research Bulletin, 173, 174-183.
https://doi.org/10.1016/j.brainresbull.2021.05.021
Perić I, Stanisavljević A, Gass P, Filipović D. Fluoxetine exerts subregion/layer specific effects on parvalbumin/GAD67 protein expression in the dorsal hippocampus of male rats showing social isolation-induced depressive-like behaviour. in Brain Research Bulletin. 2021;173:174-183.
doi:10.1016/j.brainresbull.2021.05.021 .
Perić, Ivana, Stanisavljević, Andrijana, Gass, Peter, Filipović, Dragana, "Fluoxetine exerts subregion/layer specific effects on parvalbumin/GAD67 protein expression in the dorsal hippocampus of male rats showing social isolation-induced depressive-like behaviour" in Brain Research Bulletin, 173 (2021):174-183,
https://doi.org/10.1016/j.brainresbull.2021.05.021 . .

Hippocampal synaptoproteomic changes of susceptibility and resilience of male rats to chronic social isolation

Perić, Ivana; Costina, Victor; Gass, Peter; Findeisen, Peter; Filipović, Dragana

(2021)

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 . .
1

Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria

Filipović, Dragana; Perić, Ivana; Costina, Victor; Stanisavljević, Andrijana; Gass, Peter; Findeisen, Peter

(2020)

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 . .
1
5
5
5

Fluoxetine modulates neuronal activity in stress-related limbic areas of adult rats subjected to the chronic social isolation

Stanisavljević, Andrijana; Perić, Ivana; Gass, Peter; Inta, Dragos; Lang, Undine E.; Borgwardt, Stefan; Filipović, Dragana

(2020)

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 . .
1
2
2
2

Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression

Perić, Ivana; Costina, Victor; Findeisen, Peter; Gass, Peter; Filipović, Dragana

(2020)

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 . .
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5

Tianeptine antagonizes the reduction of PV+ and GAD67 cells number in dorsal hippocampus of socially isolated rats

Perić, Ivana; Stanisavljević, Andrijana; Inta, Dragos; Gass, Peter; Undine, Lang E.; Borgwardt, Stefan; Filipović, Dragana

(2019)

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 . .
10
9
9

Brain Sub/Region-Specific Effects of Olanzapine on c-Fos Expression of Chronically Socially Isolated Rats

Stanisavljević, Andrijana; Perić, Ivana; Gass, Peter; Inta, Dragos; Lang, Undine E.; Borgwardt, Stefan; Filipović, Dragana

(2019)

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 . .
16
15
15

Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats

Todorović, Nevena; Mićić, Bojana; Schwirtlich, Marija; Stevanović, Milena J.; Filipović, Dragana

(2019)

TY  - JOUR
AU  - Todorović, Nevena
AU  - Mićić, Bojana
AU  - Schwirtlich, Marija
AU  - Stevanović, Milena J.
AU  - Filipović, Dragana
PY  - 2019
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0306452218307322
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7982
AB  - Dysregulation of GABAergic system is becoming increasingly associated with depression, psychiatric disorder that imposes severe clinical, social and economic burden. Special attention is paid to the fast-spiking parvalbumin-positive (PV+) interneurons, GABAergic neurons which are highly susceptible to redox dysregulation and oxidative stress and implicated in a variety of psychiatric diseases. Here we analyzed the number of PV+ and cleaved caspase-3-positive (CC3+) cells in the rat medial prefrontal cortical (mPFC) subregions following chronic social isolation (CSIS), an animal model of depression and schizophrenia. Also, we examined potential protective effects of antidepressant fluoxetine (FLX) and atypical antipsychotic clozapine (CLZ) on the number of these cells in mPFC subregions, when applied parallel with CSIS in doses that correspond to therapeutically effective ones in patients. Immunofluorescence analysis revealed decreased number of PV+ cells in cingulate cortex area 1, prelimbic area (PrL), infralimbic area (IL) and dorsal peduncular cortex of the mPFC in isolated rats, which coincided with depressive- and anxiety-like behaviors. In addition, CSIS-induced increase in the number of CC3+ cells was detected in aforementioned subregions of mPFC. Treatments with either FLX or CLZ prevented behavioral changes, decrease in PV+ and increase in CC3+ cell numbers in PrL and IL subregions in isolated rats. These results indicate the importance of intact GABAergic signaling in these areas for resistance against CSIS-induced behavioral changes, as well as subregion-specific protective effects of FLX and CLZ in mPFC of CSIS rats. © 2018 IBRO
T2  - Neuroscience
T1  - Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats
VL  - 396
SP  - 24
EP  - 35
DO  - 10.1016/j.neuroscience.2018.11.008
ER  - 
@article{
author = "Todorović, Nevena and Mićić, Bojana and Schwirtlich, Marija and Stevanović, Milena J. and Filipović, Dragana",
year = "2019",
abstract = "Dysregulation of GABAergic system is becoming increasingly associated with depression, psychiatric disorder that imposes severe clinical, social and economic burden. Special attention is paid to the fast-spiking parvalbumin-positive (PV+) interneurons, GABAergic neurons which are highly susceptible to redox dysregulation and oxidative stress and implicated in a variety of psychiatric diseases. Here we analyzed the number of PV+ and cleaved caspase-3-positive (CC3+) cells in the rat medial prefrontal cortical (mPFC) subregions following chronic social isolation (CSIS), an animal model of depression and schizophrenia. Also, we examined potential protective effects of antidepressant fluoxetine (FLX) and atypical antipsychotic clozapine (CLZ) on the number of these cells in mPFC subregions, when applied parallel with CSIS in doses that correspond to therapeutically effective ones in patients. Immunofluorescence analysis revealed decreased number of PV+ cells in cingulate cortex area 1, prelimbic area (PrL), infralimbic area (IL) and dorsal peduncular cortex of the mPFC in isolated rats, which coincided with depressive- and anxiety-like behaviors. In addition, CSIS-induced increase in the number of CC3+ cells was detected in aforementioned subregions of mPFC. Treatments with either FLX or CLZ prevented behavioral changes, decrease in PV+ and increase in CC3+ cell numbers in PrL and IL subregions in isolated rats. These results indicate the importance of intact GABAergic signaling in these areas for resistance against CSIS-induced behavioral changes, as well as subregion-specific protective effects of FLX and CLZ in mPFC of CSIS rats. © 2018 IBRO",
journal = "Neuroscience",
title = "Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats",
volume = "396",
pages = "24-35",
doi = "10.1016/j.neuroscience.2018.11.008"
}
Todorović, N., Mićić, B., Schwirtlich, M., Stevanović, M. J.,& Filipović, D.. (2019). Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats. in Neuroscience, 396, 24-35.
https://doi.org/10.1016/j.neuroscience.2018.11.008
Todorović N, Mićić B, Schwirtlich M, Stevanović MJ, Filipović D. Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats. in Neuroscience. 2019;396:24-35.
doi:10.1016/j.neuroscience.2018.11.008 .
Todorović, Nevena, Mićić, Bojana, Schwirtlich, Marija, Stevanović, Milena J., Filipović, Dragana, "Subregion-specific Protective Effects of Fluoxetine and Clozapine on Parvalbumin Expression in Medial Prefrontal Cortex of Chronically Isolated Rats" in Neuroscience, 396 (2019):24-35,
https://doi.org/10.1016/j.neuroscience.2018.11.008 . .
16
14
13

Clozapine increased c-Fos protein expression in several brain subregions of socially isolated rats

Stanisavljević, Andrijana; Perić, Ivana; Bernardi, Rick E.; Gass, Peter; Filipović, Dragana

(2019)

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 . .
9
7
7

Chronic Treatment with Fluoxetine or Clozapine of Socially Isolated Rats Prevents Subsector-Specific Reduction of Parvalbumin Immunoreactive Cells in the Hippocampus

(2018)

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 . .
1
33
31
30

Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of action

Perić, Ivana; Costina, Victor; Stanisavljević, Andrijana; Findeisen, Peter; Filipović, Dragana

(2018)

TY  - JOUR
AU  - Perić, Ivana
AU  - Costina, Victor
AU  - Stanisavljević, Andrijana
AU  - Findeisen, Peter
AU  - Filipović, Dragana
PY  - 2018
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0028390818301461
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7913
AB  - Due to the severity of depressive symptoms, there remains a necessity in defining the underlying mechanisms of depression and the precise actions of antidepressants in alleviating these symptoms. Proteomics is a powerful and promising tool for discovering novel pathways of cellular responses to disease and treatment. As chronic social isolation (CSIS) is a valuable animal model for studying depression, we performed a comparative subproteomic study of rat hippocampus to explore the effect of six weeks of CSIS and the therapeutic effect of chronic fluoxetine (Flx) treatment (last three weeks of CSIS; 15 mg/kg/day). Behaviorally, Flx treatment normalized the decreased sucrose preference and increased marble burying results resulting from CSIS, indicative of a FLX-induced attenuation of both anhedonia and anxiety. An analysis of cytosolic and nonsynaptic mitochondrial subproteome patterns revealed that CSIS resulted in down-regulation of proteins involved in mitochondrial transport and energy processes, primarily tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Chronic Flx treatment resulted in an up-regulation of CSIS-altered proteins and additional expression of other transporter and energy-involved proteins. Immunohistochemical analysis revealed hippocampal subregion-specific effects of CSIS and/or Flx treatment on selective protein expressions. (C) 2018 Elsevier Ltd. All rights reserved.
T2  - Neuropharmacology
T1  - Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of action
VL  - 135
SP  - 268
EP  - 283
DO  - 10.1016/j.neuropharm.2018.03.034
ER  - 
@article{
author = "Perić, Ivana and Costina, Victor and Stanisavljević, Andrijana and Findeisen, Peter and Filipović, Dragana",
year = "2018",
abstract = "Due to the severity of depressive symptoms, there remains a necessity in defining the underlying mechanisms of depression and the precise actions of antidepressants in alleviating these symptoms. Proteomics is a powerful and promising tool for discovering novel pathways of cellular responses to disease and treatment. As chronic social isolation (CSIS) is a valuable animal model for studying depression, we performed a comparative subproteomic study of rat hippocampus to explore the effect of six weeks of CSIS and the therapeutic effect of chronic fluoxetine (Flx) treatment (last three weeks of CSIS; 15 mg/kg/day). Behaviorally, Flx treatment normalized the decreased sucrose preference and increased marble burying results resulting from CSIS, indicative of a FLX-induced attenuation of both anhedonia and anxiety. An analysis of cytosolic and nonsynaptic mitochondrial subproteome patterns revealed that CSIS resulted in down-regulation of proteins involved in mitochondrial transport and energy processes, primarily tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Chronic Flx treatment resulted in an up-regulation of CSIS-altered proteins and additional expression of other transporter and energy-involved proteins. Immunohistochemical analysis revealed hippocampal subregion-specific effects of CSIS and/or Flx treatment on selective protein expressions. (C) 2018 Elsevier Ltd. All rights reserved.",
journal = "Neuropharmacology",
title = "Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of action",
volume = "135",
pages = "268-283",
doi = "10.1016/j.neuropharm.2018.03.034"
}
Perić, I., Costina, V., Stanisavljević, A., Findeisen, P.,& Filipović, D.. (2018). Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of action. in Neuropharmacology, 135, 268-283.
https://doi.org/10.1016/j.neuropharm.2018.03.034
Perić I, Costina V, Stanisavljević A, Findeisen P, Filipović D. Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of action. in Neuropharmacology. 2018;135:268-283.
doi:10.1016/j.neuropharm.2018.03.034 .
Perić, Ivana, Costina, Victor, Stanisavljević, Andrijana, Findeisen, Peter, Filipović, Dragana, "Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of action" in Neuropharmacology, 135 (2018):268-283,
https://doi.org/10.1016/j.neuropharm.2018.03.034 . .
2
22
18
20

Oxidative and nitrosative stress pathways in the brain of socially isolated adult male rats demonstrating depressive- and anxiety-like symptoms

Filipović, Dragana; Todorović, Nevena; Bernardi, Rick E.; Gass, Peter

(2017)

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 . .
1
74
62
67

Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria

Filipović, Dragana; Costina, Victor; Perić, Ivana; Stanisavljević, Andrijana; Findeisen, Peter

(2017)

TY  - JOUR
AU  - Filipović, Dragana
AU  - Costina, Victor
AU  - Perić, Ivana
AU  - Stanisavljević, Andrijana
AU  - Findeisen, Peter
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1441
AB  - Fluoxetine (Flx) is the principal treatment for depression; however, the precise mechanisms of its actions remain elusive. Our aim was to identify protein expression changes within rat hippocampus regulated by chronic Flx treatment versus vehicle-controls using proteomics. Fluoxetine-hydrohloride (15 mg/kg) was administered daily to adult male Wistar rats for 3 weeks, and cytosolic and nonsynaptic mitochondrial hippocampal proteomes were analyzed. All differentially expressed proteins were functionally annotated according to biological process and molecular function using Uniprot and Blast2GO. Our comparative study revealed that in cytosolic and nonsynaptic mitochondrial fractions, 60 and 3 proteins respectively, were down-regulated, and 23 and 60 proteins, respectively, were up-regulated. Proteins differentially regulated in cytosolic and nonsynaptic mitochondrial fractions were primarily related to cellular and metabolic processes. Of the identified proteins, the expressions of calretinin and parvalbumine were confirmed. The predominant molecular functions of differentially expressed proteins in both cell hippocampal fractions were binding and catalytic activity. Most differentially expressed proteins in nonsynaptic mitochondria were catalytic enzymes involved in the pyruvate metabolism, citric acid cycle, oxidative phosphorylation, ATP synthesis, ATP transduction and glutamate metabolism. Results indicate that chronic Flx treatment may influence proteins involved in calcium signaling, cytoskeletal structure, chaperone system and stimulates energy metabolism via the upregulation of GAPDH expression in cytoplasm, as well as directing energy metabolism toward the citric acid cycle and oxidative phosphorylation in nonsynaptic mitochondria. This approach provides new insight into the chronic effects of Flx treatment on protein expression in a key brain region associated with stress response and memory. (C) 2017 Elsevier B.V. All rights reserved.
T2  - Brain Research
T1  - Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria
VL  - 1659
SP  - 41
EP  - 54
DO  - 10.1016/j.brainres.2017.01.025
ER  - 
@article{
author = "Filipović, Dragana and Costina, Victor and Perić, Ivana and Stanisavljević, Andrijana and Findeisen, Peter",
year = "2017",
abstract = "Fluoxetine (Flx) is the principal treatment for depression; however, the precise mechanisms of its actions remain elusive. Our aim was to identify protein expression changes within rat hippocampus regulated by chronic Flx treatment versus vehicle-controls using proteomics. Fluoxetine-hydrohloride (15 mg/kg) was administered daily to adult male Wistar rats for 3 weeks, and cytosolic and nonsynaptic mitochondrial hippocampal proteomes were analyzed. All differentially expressed proteins were functionally annotated according to biological process and molecular function using Uniprot and Blast2GO. Our comparative study revealed that in cytosolic and nonsynaptic mitochondrial fractions, 60 and 3 proteins respectively, were down-regulated, and 23 and 60 proteins, respectively, were up-regulated. Proteins differentially regulated in cytosolic and nonsynaptic mitochondrial fractions were primarily related to cellular and metabolic processes. Of the identified proteins, the expressions of calretinin and parvalbumine were confirmed. The predominant molecular functions of differentially expressed proteins in both cell hippocampal fractions were binding and catalytic activity. Most differentially expressed proteins in nonsynaptic mitochondria were catalytic enzymes involved in the pyruvate metabolism, citric acid cycle, oxidative phosphorylation, ATP synthesis, ATP transduction and glutamate metabolism. Results indicate that chronic Flx treatment may influence proteins involved in calcium signaling, cytoskeletal structure, chaperone system and stimulates energy metabolism via the upregulation of GAPDH expression in cytoplasm, as well as directing energy metabolism toward the citric acid cycle and oxidative phosphorylation in nonsynaptic mitochondria. This approach provides new insight into the chronic effects of Flx treatment on protein expression in a key brain region associated with stress response and memory. (C) 2017 Elsevier B.V. All rights reserved.",
journal = "Brain Research",
title = "Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria",
volume = "1659",
pages = "41-54",
doi = "10.1016/j.brainres.2017.01.025"
}
Filipović, D., Costina, V., Perić, I., Stanisavljević, A.,& Findeisen, P.. (2017). Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria. in Brain Research, 1659, 41-54.
https://doi.org/10.1016/j.brainres.2017.01.025
Filipović D, Costina V, Perić I, Stanisavljević A, Findeisen P. Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria. in Brain Research. 2017;1659:41-54.
doi:10.1016/j.brainres.2017.01.025 .
Filipović, Dragana, Costina, Victor, Perić, Ivana, Stanisavljević, Andrijana, Findeisen, Peter, "Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria" in Brain Research, 1659 (2017):41-54,
https://doi.org/10.1016/j.brainres.2017.01.025 . .
1
25
20
20

Olanzapine alleviates oxidative stress in the liver of socially isolated rats

Stanisavljević, Andrijana; Perić, Ivana; Pantelić, Marija; Filipović, Dragana

(2017)

TY  - JOUR
AU  - Stanisavljević, Andrijana
AU  - Perić, Ivana
AU  - Pantelić, Marija
AU  - Filipović, Dragana
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1592
AB  - Olanzapine, an antipsychotic drug, is used to treat depressive disorder, but its effects on the liver, the main site of drug metabolism, still remain elusive. We studied the effects of 3 weeks of olanzapine treatment (7.5 mg/kg per day) on the malondialdehyde (MDA) and protein carbonyl (PCO) contents, protein expression of copper/zinc superoxide dismutase (CuZnSOD), and activity of total superoxide dismutase (SOD), as well as catalase (CAT) protein expression and activity levels in the liver cytosol of rats exposed to 6 weeks of chronic social isolation (CSIS), which causes depressive- and anxiety-like behaviors. Increased cytosolic MDA in CSIS rats (vehicle-or olanzapine-treated) indicated hepatic oxidative stress. Increase in PCO and CAT activity associated with unchanged total SOD activity following CSIS also confirm the presence of oxidative stress. Chronic olanzapine treatment in CSIS prevented increase in PCO without an effect on MDA content. Increased SOD activity in olanzapine-treated (controls and CSIS) groups compared with corresponding vehicle-treated groups and decreased CAT activity in olanzapine-treated CSIS rats compared with vehicle-treated CSIS group was found. The data suggest that chronic olanzapine treatment has a protective effect on hepatic protein oxidation and improves antioxidant defense. The beneficial effects of olanzapine may be due to its free radical scavenging properties and antioxidant activity.
T2  - Canadian Journal of Physiology and Pharmacology
T1  - Olanzapine alleviates oxidative stress in the liver of socially isolated rats
VL  - 95
IS  - 6
SP  - 634
EP  - 640
DO  - 10.1139/cjpp-2016-0598
ER  - 
@article{
author = "Stanisavljević, Andrijana and Perić, Ivana and Pantelić, Marija and Filipović, Dragana",
year = "2017",
abstract = "Olanzapine, an antipsychotic drug, is used to treat depressive disorder, but its effects on the liver, the main site of drug metabolism, still remain elusive. We studied the effects of 3 weeks of olanzapine treatment (7.5 mg/kg per day) on the malondialdehyde (MDA) and protein carbonyl (PCO) contents, protein expression of copper/zinc superoxide dismutase (CuZnSOD), and activity of total superoxide dismutase (SOD), as well as catalase (CAT) protein expression and activity levels in the liver cytosol of rats exposed to 6 weeks of chronic social isolation (CSIS), which causes depressive- and anxiety-like behaviors. Increased cytosolic MDA in CSIS rats (vehicle-or olanzapine-treated) indicated hepatic oxidative stress. Increase in PCO and CAT activity associated with unchanged total SOD activity following CSIS also confirm the presence of oxidative stress. Chronic olanzapine treatment in CSIS prevented increase in PCO without an effect on MDA content. Increased SOD activity in olanzapine-treated (controls and CSIS) groups compared with corresponding vehicle-treated groups and decreased CAT activity in olanzapine-treated CSIS rats compared with vehicle-treated CSIS group was found. The data suggest that chronic olanzapine treatment has a protective effect on hepatic protein oxidation and improves antioxidant defense. The beneficial effects of olanzapine may be due to its free radical scavenging properties and antioxidant activity.",
journal = "Canadian Journal of Physiology and Pharmacology",
title = "Olanzapine alleviates oxidative stress in the liver of socially isolated rats",
volume = "95",
number = "6",
pages = "634-640",
doi = "10.1139/cjpp-2016-0598"
}
Stanisavljević, A., Perić, I., Pantelić, M.,& Filipović, D.. (2017). Olanzapine alleviates oxidative stress in the liver of socially isolated rats. in Canadian Journal of Physiology and Pharmacology, 95(6), 634-640.
https://doi.org/10.1139/cjpp-2016-0598
Stanisavljević A, Perić I, Pantelić M, Filipović D. Olanzapine alleviates oxidative stress in the liver of socially isolated rats. in Canadian Journal of Physiology and Pharmacology. 2017;95(6):634-640.
doi:10.1139/cjpp-2016-0598 .
Stanisavljević, Andrijana, Perić, Ivana, Pantelić, Marija, Filipović, Dragana, "Olanzapine alleviates oxidative stress in the liver of socially isolated rats" in Canadian Journal of Physiology and Pharmacology, 95, no. 6 (2017):634-640,
https://doi.org/10.1139/cjpp-2016-0598 . .
9
8
9

Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines

Perić, Ivana; Stanisavljević, Andrijana; Gass, Peter; Filipović, Dragana

(2017)

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 . .
1
28
21
25

Hippocampal BDNF in physiological conditions and social isolation

Zaletel, Ivan; Filipović, Dragana; Puškaš, Nela

(2017)

TY  - JOUR
AU  - Zaletel, Ivan
AU  - Filipović, Dragana
AU  - Puškaš, Nela
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1664
AB  - Exposure of an organism to chronic psychosocial stress may affect brain-derived neurotrophic factor (BDNF) expression that has been implicated in the etiology of psychiatric disorders, such as depression. Given that depression in humans has been linked with social stress, the chronic social stress paradigms for modeling psychiatric disorders in animals have thus been developed. Chronic social isolation in animal models generally causes changes in hypothalamic-pituitary-adrenal axis functioning, associated with anxiety-and depressive-like behaviors. Also, this chronic stress causes downregulation of BDNF protein and mRNA in the hippocampus, a stress-sensitive brain region closely related to the pathophysiology of depression. In this review, we discuss the current knowledge regarding the structure, function, intracellular signaling, inter-individual differences and epigenetic regulation of BDNF in both physiological conditions and depression and changes in corticosterone levels, as a marker of stress response. Since BDNF levels are age dependent in humans and rodents, this review will also highlight the effects of adolescent and adult chronic social isolation models of both genders on the BDNF expression.
T2  - Reviews in the Neurosciences
T1  - Hippocampal BDNF in physiological conditions and social isolation
VL  - 28
IS  - 6
SP  - 675
EP  - 692
DO  - 10.1515/revneuro-2016-0072
ER  - 
@article{
author = "Zaletel, Ivan and Filipović, Dragana and Puškaš, Nela",
year = "2017",
abstract = "Exposure of an organism to chronic psychosocial stress may affect brain-derived neurotrophic factor (BDNF) expression that has been implicated in the etiology of psychiatric disorders, such as depression. Given that depression in humans has been linked with social stress, the chronic social stress paradigms for modeling psychiatric disorders in animals have thus been developed. Chronic social isolation in animal models generally causes changes in hypothalamic-pituitary-adrenal axis functioning, associated with anxiety-and depressive-like behaviors. Also, this chronic stress causes downregulation of BDNF protein and mRNA in the hippocampus, a stress-sensitive brain region closely related to the pathophysiology of depression. In this review, we discuss the current knowledge regarding the structure, function, intracellular signaling, inter-individual differences and epigenetic regulation of BDNF in both physiological conditions and depression and changes in corticosterone levels, as a marker of stress response. Since BDNF levels are age dependent in humans and rodents, this review will also highlight the effects of adolescent and adult chronic social isolation models of both genders on the BDNF expression.",
journal = "Reviews in the Neurosciences",
title = "Hippocampal BDNF in physiological conditions and social isolation",
volume = "28",
number = "6",
pages = "675-692",
doi = "10.1515/revneuro-2016-0072"
}
Zaletel, I., Filipović, D.,& Puškaš, N.. (2017). Hippocampal BDNF in physiological conditions and social isolation. in Reviews in the Neurosciences, 28(6), 675-692.
https://doi.org/10.1515/revneuro-2016-0072
Zaletel I, Filipović D, Puškaš N. Hippocampal BDNF in physiological conditions and social isolation. in Reviews in the Neurosciences. 2017;28(6):675-692.
doi:10.1515/revneuro-2016-0072 .
Zaletel, Ivan, Filipović, Dragana, Puškaš, Nela, "Hippocampal BDNF in physiological conditions and social isolation" in Reviews in the Neurosciences, 28, no. 6 (2017):675-692,
https://doi.org/10.1515/revneuro-2016-0072 . .
1
45
39
41

The antidepressant- and anxiolytic-like effects of fluoxetine and clozapine in chronically isolated rats involve inhibition of hippocampal TNF-alpha

Todorović, Nevena; Filipović, Dragana

(2017)

TY  - JOUR
AU  - Todorović, Nevena
AU  - Filipović, Dragana
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1875
AB  - Brain oxidative stress and neuroinflammation are implicated in psychiatric disorders. Thus, it is important to investigate the effects of individual psychotropic agents on antioxidative defense and proinflammatory mediators in brain regions associated with these disorders. Psychosocial stress is recognized as a threat to mental health, and the hippocampus is a primary target of stress-related damage. Chronic social isolation (CSIS) is a mild psychosocial stress used to model the pathophysiology of depression. We examined the antioxidative and anti-inflammatory potential of the antidepressant fluoxetine (FLX) and atypical antipsychotic clozapine (CLZ) in the hippocampus in the CSIS model of depression. We measured the effects of FLX and CLZ on depressive- and anxiety-like behaviors in non-stressed rats and rats exposed to 21d of CSIS. We further evaluated the content of reduced glutathione (GSH), the protein expression and activity of the GSH-related enzymes, the subcellular localization of nuclear factor-kappa B (NF-kappa B)and protein levels of proinflammatory mediators cyclooxygenase-2 (COX-2), interleukin-lbeta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) in these groups of rats. CSIS resulted in an increase in depressive- and anxiety-like behaviors that corresponded with compromised glutathione peroxidase (GPx)-mediated antioxidative defense and increased TNF-alpha, but not with changes in NF-kappa B, IL-1 beta and COX-2 levels. FLX and CLZ, applied during CSIS, prevented the behavioral changes associated with CSIS, and inhibited the increase in TNF-alpha, but did not affect GPx-mediated antioxidative defense. Furthermore, both drugs decreased hippocampal GPx activity when applied to non-stressed rats. These results emphasize the significance of hippocampal TNF-alpha-mediated proinflammmatory signaling in the pathophysiology of depressive symptoms and the importance of the anti-inflammatory action of both FLX and CLZ in the prevention of these symptoms.
T2  - Pharmacology Biochemistry and Behavior
T1  - The antidepressant- and anxiolytic-like effects of fluoxetine and clozapine in chronically isolated rats involve inhibition of hippocampal TNF-alpha
VL  - 163
SP  - 57
EP  - 65
DO  - 10.1016/j.pbb.2017.10.006
ER  - 
@article{
author = "Todorović, Nevena and Filipović, Dragana",
year = "2017",
abstract = "Brain oxidative stress and neuroinflammation are implicated in psychiatric disorders. Thus, it is important to investigate the effects of individual psychotropic agents on antioxidative defense and proinflammatory mediators in brain regions associated with these disorders. Psychosocial stress is recognized as a threat to mental health, and the hippocampus is a primary target of stress-related damage. Chronic social isolation (CSIS) is a mild psychosocial stress used to model the pathophysiology of depression. We examined the antioxidative and anti-inflammatory potential of the antidepressant fluoxetine (FLX) and atypical antipsychotic clozapine (CLZ) in the hippocampus in the CSIS model of depression. We measured the effects of FLX and CLZ on depressive- and anxiety-like behaviors in non-stressed rats and rats exposed to 21d of CSIS. We further evaluated the content of reduced glutathione (GSH), the protein expression and activity of the GSH-related enzymes, the subcellular localization of nuclear factor-kappa B (NF-kappa B)and protein levels of proinflammatory mediators cyclooxygenase-2 (COX-2), interleukin-lbeta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) in these groups of rats. CSIS resulted in an increase in depressive- and anxiety-like behaviors that corresponded with compromised glutathione peroxidase (GPx)-mediated antioxidative defense and increased TNF-alpha, but not with changes in NF-kappa B, IL-1 beta and COX-2 levels. FLX and CLZ, applied during CSIS, prevented the behavioral changes associated with CSIS, and inhibited the increase in TNF-alpha, but did not affect GPx-mediated antioxidative defense. Furthermore, both drugs decreased hippocampal GPx activity when applied to non-stressed rats. These results emphasize the significance of hippocampal TNF-alpha-mediated proinflammmatory signaling in the pathophysiology of depressive symptoms and the importance of the anti-inflammatory action of both FLX and CLZ in the prevention of these symptoms.",
journal = "Pharmacology Biochemistry and Behavior",
title = "The antidepressant- and anxiolytic-like effects of fluoxetine and clozapine in chronically isolated rats involve inhibition of hippocampal TNF-alpha",
volume = "163",
pages = "57-65",
doi = "10.1016/j.pbb.2017.10.006"
}
Todorović, N.,& Filipović, D.. (2017). The antidepressant- and anxiolytic-like effects of fluoxetine and clozapine in chronically isolated rats involve inhibition of hippocampal TNF-alpha. in Pharmacology Biochemistry and Behavior, 163, 57-65.
https://doi.org/10.1016/j.pbb.2017.10.006
Todorović N, Filipović D. The antidepressant- and anxiolytic-like effects of fluoxetine and clozapine in chronically isolated rats involve inhibition of hippocampal TNF-alpha. in Pharmacology Biochemistry and Behavior. 2017;163:57-65.
doi:10.1016/j.pbb.2017.10.006 .
Todorović, Nevena, Filipović, Dragana, "The antidepressant- and anxiolytic-like effects of fluoxetine and clozapine in chronically isolated rats involve inhibition of hippocampal TNF-alpha" in Pharmacology Biochemistry and Behavior, 163 (2017):57-65,
https://doi.org/10.1016/j.pbb.2017.10.006 . .
1
21
21
19

Prefrontal Cortical Glutathione-Dependent Defense and Proinflammatory Mediators in Chronically Isolated Rats: Modulation By Fluoxetine Or Clozapine

Todorović, Nevena; Filipović, Dragana

(2017)

TY  - JOUR
AU  - Todorović, Nevena
AU  - Filipović, Dragana
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1613
AB  - Chronic psychosocial stress modulates brain antioxidant systems and causes neuroinflammation that plays a role in the pathophysiology of depression. Although the antidepressant fluoxetine (FLX) represents the first-line treatment for depression and the atypical antipsychotic clozapine (CLZ) is considered as a second-line treatment for psychotic disorders, the downstream mechanisms of action of these treatments, beyond serotonergic or dopaminergic signaling, remain elusive. We examined behavioral changes, glutathione (GSH)-dependent defense and levels of proinflammatory mediators in the prefrontal cortex (PFC) of adult male Wistar rats exposed to 21 days of chronic social isolation (CSIS). We also tested the ability of FLX (15 mg/kg/day) or CLZ (20 mg/kg/day), applied during CSIS, to prevent stress-induced changes. CSIS caused depressive-and anxiety-like behaviors, compromised GSH-dependent defense, and induced nuclear factor-kappa B (NF-kappa B) activation with a concomitant increase in cytosolic levels of proinflammatory mediators cyclooxigenase-2, interleukin-1beta and tumor necrosis factor-alpha in the PFC. NF-kappa B activation and proinflammatory response in the PFC were not found in CSIS rats treated with FLX or CLZ. In contrast, only FLX preserved GSH content in CSIS rats. CLZ not only failed to protect against CSIS-induced GSH depletion, but it diminished its levels when applied to non-stressed rats. In conclusion, prefrontal cortical GSH depletion and the proinflammatory response underlying depressive-and anxiety-like states induced by CSIS were prevented by FLX. The protective effect of CLZ, which was equally effective as FLX on the behavioral level, was limited to proinflammatory components. Hence, different mechanisms underlie the protective effects of these two drugs in CSIS rats. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
T2  - Neuroscience
T1  - Prefrontal Cortical Glutathione-Dependent Defense and Proinflammatory Mediators in Chronically Isolated Rats: Modulation By Fluoxetine Or Clozapine
VL  - 355
SP  - 49
EP  - 60
DO  - 10.1016/j.neuroscience.2017.04.044
ER  - 
@article{
author = "Todorović, Nevena and Filipović, Dragana",
year = "2017",
abstract = "Chronic psychosocial stress modulates brain antioxidant systems and causes neuroinflammation that plays a role in the pathophysiology of depression. Although the antidepressant fluoxetine (FLX) represents the first-line treatment for depression and the atypical antipsychotic clozapine (CLZ) is considered as a second-line treatment for psychotic disorders, the downstream mechanisms of action of these treatments, beyond serotonergic or dopaminergic signaling, remain elusive. We examined behavioral changes, glutathione (GSH)-dependent defense and levels of proinflammatory mediators in the prefrontal cortex (PFC) of adult male Wistar rats exposed to 21 days of chronic social isolation (CSIS). We also tested the ability of FLX (15 mg/kg/day) or CLZ (20 mg/kg/day), applied during CSIS, to prevent stress-induced changes. CSIS caused depressive-and anxiety-like behaviors, compromised GSH-dependent defense, and induced nuclear factor-kappa B (NF-kappa B) activation with a concomitant increase in cytosolic levels of proinflammatory mediators cyclooxigenase-2, interleukin-1beta and tumor necrosis factor-alpha in the PFC. NF-kappa B activation and proinflammatory response in the PFC were not found in CSIS rats treated with FLX or CLZ. In contrast, only FLX preserved GSH content in CSIS rats. CLZ not only failed to protect against CSIS-induced GSH depletion, but it diminished its levels when applied to non-stressed rats. In conclusion, prefrontal cortical GSH depletion and the proinflammatory response underlying depressive-and anxiety-like states induced by CSIS were prevented by FLX. The protective effect of CLZ, which was equally effective as FLX on the behavioral level, was limited to proinflammatory components. Hence, different mechanisms underlie the protective effects of these two drugs in CSIS rats. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.",
journal = "Neuroscience",
title = "Prefrontal Cortical Glutathione-Dependent Defense and Proinflammatory Mediators in Chronically Isolated Rats: Modulation By Fluoxetine Or Clozapine",
volume = "355",
pages = "49-60",
doi = "10.1016/j.neuroscience.2017.04.044"
}
Todorović, N.,& Filipović, D.. (2017). Prefrontal Cortical Glutathione-Dependent Defense and Proinflammatory Mediators in Chronically Isolated Rats: Modulation By Fluoxetine Or Clozapine. in Neuroscience, 355, 49-60.
https://doi.org/10.1016/j.neuroscience.2017.04.044
Todorović N, Filipović D. Prefrontal Cortical Glutathione-Dependent Defense and Proinflammatory Mediators in Chronically Isolated Rats: Modulation By Fluoxetine Or Clozapine. in Neuroscience. 2017;355:49-60.
doi:10.1016/j.neuroscience.2017.04.044 .
Todorović, Nevena, Filipović, Dragana, "Prefrontal Cortical Glutathione-Dependent Defense and Proinflammatory Mediators in Chronically Isolated Rats: Modulation By Fluoxetine Or Clozapine" in Neuroscience, 355 (2017):49-60,
https://doi.org/10.1016/j.neuroscience.2017.04.044 . .
1
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11
11

The effects of fluoxetine on hippocampal antioxidative defense in depressive-like rats

Perić, Ivana; Todorović, Nevena; Stanisavljević, Andrijana; Đorđević, Neda O.; Filipović, Dragana

(Society of Physical Chemists of Serbia, 2016)

TY  - CONF
AU  - Perić, Ivana
AU  - Todorović, Nevena
AU  - Stanisavljević, Andrijana
AU  - Đorđević, Neda O.
AU  - Filipović, Dragana
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9200
AB  - Exposure   of   an   organism   to   chronic   social   isolation   (CSIS)   causes modulation  of  antioxidant  defense  system  in  the  brain  which  has  been shown to have important role in depression. Fluoxetine (Flx) is the first-line treatment  for  depression;  however,  precise  mechanism  of  its  action  still remains  elusive.  The  aim  of  this  study  was  to  investigate  the  effect  of  3 weeks  of  Flx  treatment  on  malondialdehyde  (MDA)  level,  an  oxidative stress parameter as well as on the activities of GSH-dependent antioxidative enzymes in the hippocampus of rats exposed to 6 weeks of CSIS. Increased MDA content following  CSIS and Flx treatment  (controls or CSIS) of rats, suggests  on  hippocampal  oxidative  damage.  CSIS  induced  reduction  of hippocampal  glutathione-S-transferase  that  was  reversed  by  Flx  treatment, as  well  as  an  increase  in  glutathione  peroxidase/reductase  activities.  The present  study  contributes  to  our  understanding  of  the  mechanisms  that underlie the antidepressant activity of Flx in rats exposed to CSIS, an animal model of depression.
PB  - Society of Physical Chemists of Serbia
C3  - Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry
T1  - The effects of fluoxetine on hippocampal antioxidative defense in depressive-like rats
SP  - 435
EP  - 438
ER  - 
@conference{
author = "Perić, Ivana and Todorović, Nevena and Stanisavljević, Andrijana and Đorđević, Neda O. and Filipović, Dragana",
year = "2016",
abstract = "Exposure   of   an   organism   to   chronic   social   isolation   (CSIS)   causes modulation  of  antioxidant  defense  system  in  the  brain  which  has  been shown to have important role in depression. Fluoxetine (Flx) is the first-line treatment  for  depression;  however,  precise  mechanism  of  its  action  still remains  elusive.  The  aim  of  this  study  was  to  investigate  the  effect  of  3 weeks  of  Flx  treatment  on  malondialdehyde  (MDA)  level,  an  oxidative stress parameter as well as on the activities of GSH-dependent antioxidative enzymes in the hippocampus of rats exposed to 6 weeks of CSIS. Increased MDA content following  CSIS and Flx treatment  (controls or CSIS) of rats, suggests  on  hippocampal  oxidative  damage.  CSIS  induced  reduction  of hippocampal  glutathione-S-transferase  that  was  reversed  by  Flx  treatment, as  well  as  an  increase  in  glutathione  peroxidase/reductase  activities.  The present  study  contributes  to  our  understanding  of  the  mechanisms  that underlie the antidepressant activity of Flx in rats exposed to CSIS, an animal model of depression.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry",
title = "The effects of fluoxetine on hippocampal antioxidative defense in depressive-like rats",
pages = "435-438"
}
Perić, I., Todorović, N., Stanisavljević, A., Đorđević, N. O.,& Filipović, D.. (2016). The effects of fluoxetine on hippocampal antioxidative defense in depressive-like rats. in Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry
Society of Physical Chemists of Serbia., 435-438.
Perić I, Todorović N, Stanisavljević A, Đorđević NO, Filipović D. The effects of fluoxetine on hippocampal antioxidative defense in depressive-like rats. in Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry. 2016;:435-438..
Perić, Ivana, Todorović, Nevena, Stanisavljević, Andrijana, Đorđević, Neda O., Filipović, Dragana, "The effects of fluoxetine on hippocampal antioxidative defense in depressive-like rats" in Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry (2016):435-438.

Olanzapine intensifies lipid peroxidation and modulates catalase activity in liver of social isolated rats

Stanisavljević, Andrijana; Perić, Ivana; Todorović, Nevena; Đorđević, Neda O.; Filipović, Dragana

(Society of Physical Chemists of Serbia, 2016)

TY  - CONF
AU  - Stanisavljević, Andrijana
AU  - Perić, Ivana
AU  - Todorović, Nevena
AU  - Đorđević, Neda O.
AU  - Filipović, Dragana
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9203
AB  - Olanzapine  is  an  antipsychotic  proved  to  be  effective  in stress  associated psychiatric diseases, but its effect on the liver, main site of drug metabolism,still  remain  unclear.  We  investigated  the  effects  of  chronic  treatment  of olanzapine   (three-week)   on   the   malondialdehyde   (MDA)   content   and protein expression and activity of antioxidant enzyme catalase (CAT) in the liver of rats exposed to chronic social isolation (CSIS) (six-week), an animal model of depression. The increased cytosolic MDA content in both vehicle-and  olanzapine-treated  CSIS  animals  suggests  oxidative  stress. Increased CAT  activityin  vehicle-treated  CSIS  animals,  which  was  not  consistent with   its   protein   expression,   suggests   induction   of   antioxidant   defense mechanisms,while  olanzapine  significantly  reduced  CAT  activity  in  CSIS group.   Data   revealed   that   although   olanzapine   treatment   reversed   the alterations  in  CAT  activity,  it  has the  ability  to  cause  hepatotoxicity,  as indicatedby increased MDA content.
PB  - Society of Physical Chemists of Serbia
C3  - Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry
T1  - Olanzapine intensifies lipid peroxidation and modulates catalase activity in liver of social isolated rats
SP  - 439
EP  - 442
ER  - 
@conference{
author = "Stanisavljević, Andrijana and Perić, Ivana and Todorović, Nevena and Đorđević, Neda O. and Filipović, Dragana",
year = "2016",
abstract = "Olanzapine  is  an  antipsychotic  proved  to  be  effective  in stress  associated psychiatric diseases, but its effect on the liver, main site of drug metabolism,still  remain  unclear.  We  investigated  the  effects  of  chronic  treatment  of olanzapine   (three-week)   on   the   malondialdehyde   (MDA)   content   and protein expression and activity of antioxidant enzyme catalase (CAT) in the liver of rats exposed to chronic social isolation (CSIS) (six-week), an animal model of depression. The increased cytosolic MDA content in both vehicle-and  olanzapine-treated  CSIS  animals  suggests  oxidative  stress. Increased CAT  activityin  vehicle-treated  CSIS  animals,  which  was  not  consistent with   its   protein   expression,   suggests   induction   of   antioxidant   defense mechanisms,while  olanzapine  significantly  reduced  CAT  activity  in  CSIS group.   Data   revealed   that   although   olanzapine   treatment   reversed   the alterations  in  CAT  activity,  it  has the  ability  to  cause  hepatotoxicity,  as indicatedby increased MDA content.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry",
title = "Olanzapine intensifies lipid peroxidation and modulates catalase activity in liver of social isolated rats",
pages = "439-442"
}
Stanisavljević, A., Perić, I., Todorović, N., Đorđević, N. O.,& Filipović, D.. (2016). Olanzapine intensifies lipid peroxidation and modulates catalase activity in liver of social isolated rats. in Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry
Society of Physical Chemists of Serbia., 439-442.
Stanisavljević A, Perić I, Todorović N, Đorđević NO, Filipović D. Olanzapine intensifies lipid peroxidation and modulates catalase activity in liver of social isolated rats. in Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry. 2016;:439-442..
Stanisavljević, Andrijana, Perić, Ivana, Todorović, Nevena, Đorđević, Neda O., Filipović, Dragana, "Olanzapine intensifies lipid peroxidation and modulates catalase activity in liver of social isolated rats" in Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry (2016):439-442.

Duloxetine enhances hepatic gsh-dependent defense in rats

Đorđević, Neda O.; Perić, Ivana; Stanisavljević, Andrijana; Todorović, Nevena; Filipović, Dragana

(Society of Physical Chemists of Serbia, 2016)

TY  - CONF
AU  - Đorđević, Neda O.
AU  - Perić, Ivana
AU  - Stanisavljević, Andrijana
AU  - Todorović, Nevena
AU  - Filipović, Dragana
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9205
AB  - Duloxetine  (DLX)  is  antidepressantfor  the  treatment  of  depression,but  its effect  on  the  liver,  a  primary  site  for  drug  metabolism,  has  yet  to  be determined.The  effect  of  3  weeks  of  DLX  treatment  onprotein  carbonyl groups   and   activities   of   GSH-dependent   defense   including   reduced glutathione   (GSH),   glutathione   peroxidase   (GPx)   and   glutathione   S-transferase  (GST)  in  liver  of  rats  exposed  to  6  weeks  of  chronic  social isolation  (CSIS),  an  animal  model  of  depression,  were  investigated.  CSIS induced increase in protein carbonyl content, which wasdecreasedby DLX treatment.  We  noticed  increase  in  GPx  and  GST  activity  in  DLX-treated (controls  and  CSIS)  rats  and  CSIS  group,  whereby  GPx  activity  was significantly higher in DLX-compared to vehicle-treatedCSIS rats. Results indicate protective effect of DLX against CSIS-induced oxidative damage of hepatic  proteins,  which  may  be  due  to  intensified  protective  mechanisms mediated by GSH-dependent defense.
PB  - Society of Physical Chemists of Serbia
C3  - Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry
T1  - Duloxetine enhances hepatic gsh-dependent defense in rats
SP  - 443
EP  - 446
ER  - 
@conference{
author = "Đorđević, Neda O. and Perić, Ivana and Stanisavljević, Andrijana and Todorović, Nevena and Filipović, Dragana",
year = "2016",
abstract = "Duloxetine  (DLX)  is  antidepressantfor  the  treatment  of  depression,but  its effect  on  the  liver,  a  primary  site  for  drug  metabolism,  has  yet  to  be determined.The  effect  of  3  weeks  of  DLX  treatment  onprotein  carbonyl groups   and   activities   of   GSH-dependent   defense   including   reduced glutathione   (GSH),   glutathione   peroxidase   (GPx)   and   glutathione   S-transferase  (GST)  in  liver  of  rats  exposed  to  6  weeks  of  chronic  social isolation  (CSIS),  an  animal  model  of  depression,  were  investigated.  CSIS induced increase in protein carbonyl content, which wasdecreasedby DLX treatment.  We  noticed  increase  in  GPx  and  GST  activity  in  DLX-treated (controls  and  CSIS)  rats  and  CSIS  group,  whereby  GPx  activity  was significantly higher in DLX-compared to vehicle-treatedCSIS rats. Results indicate protective effect of DLX against CSIS-induced oxidative damage of hepatic  proteins,  which  may  be  due  to  intensified  protective  mechanisms mediated by GSH-dependent defense.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry",
title = "Duloxetine enhances hepatic gsh-dependent defense in rats",
pages = "443-446"
}
Đorđević, N. O., Perić, I., Stanisavljević, A., Todorović, N.,& Filipović, D.. (2016). Duloxetine enhances hepatic gsh-dependent defense in rats. in Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry
Society of Physical Chemists of Serbia., 443-446.
Đorđević NO, Perić I, Stanisavljević A, Todorović N, Filipović D. Duloxetine enhances hepatic gsh-dependent defense in rats. in Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry. 2016;:443-446..
Đorđević, Neda O., Perić, Ivana, Stanisavljević, Andrijana, Todorović, Nevena, Filipović, Dragana, "Duloxetine enhances hepatic gsh-dependent defense in rats" in Physical chemistry 2016 : 13th international conference on fundamental and applied aspects of physical chemistry (2016):443-446.

Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats

Todorović, Nevena; Tomanović, Nada; Gass, Peter; Filipović, Dragana

(Elsevier, 2016)

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 . .
10
23
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22

Chronic stress, hippocampus and parvalbumin-positive interneurons: what do we know so far?

Zaletel, Ivan; Filipović, Dragana; Puškaš, Nela

(2016)

TY  - JOUR
AU  - Zaletel, Ivan
AU  - Filipović, Dragana
AU  - Puškaš, Nela
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1088
AB  - The hippocampus is a brain structure involved in the regulation of hypothalamic-pituitary-adrenal (HPA) axis and stress response. It plays an important role in the formation of declarative, spatial and contextual memory, as well as in the processing of emotional information. As a part of the limbic system, it is a very susceptible structure towards the effects of various stressors. The molecular mechanisms of structural and functional alternations that occur in the hippocampus under chronic stress imply an increased level of circulating glucocorticoids (GCs), which is an HPA axis response to stress. Certain data show that changes induced by chronic stress may be independent from the GCs levels, opening the possibility of existence of other poorly explored mechanisms and pathways through which stressors act. The hippocampal GABAergic parvalbumin-positive (PV+) interneurons represent an especially vulnerable population of neurons in chronic stress, which may be of key importance in the development of mood disorders. However, cellular and molecular hippocampal changes that arise as a consequence of chronic stress still represent a large and unexplored area. This review discusses the current knowledge about the PV+ interneurons of the hippocampus and the influence of chronic stress on this intriguing population of neurons.
T2  - Reviews in the Neurosciences
T1  - Chronic stress, hippocampus and parvalbumin-positive interneurons: what do we know so far?
VL  - 27
IS  - 4
SP  - 397
EP  - 409
DO  - 10.1515/revneuro-2015-0042
ER  - 
@article{
author = "Zaletel, Ivan and Filipović, Dragana and Puškaš, Nela",
year = "2016",
abstract = "The hippocampus is a brain structure involved in the regulation of hypothalamic-pituitary-adrenal (HPA) axis and stress response. It plays an important role in the formation of declarative, spatial and contextual memory, as well as in the processing of emotional information. As a part of the limbic system, it is a very susceptible structure towards the effects of various stressors. The molecular mechanisms of structural and functional alternations that occur in the hippocampus under chronic stress imply an increased level of circulating glucocorticoids (GCs), which is an HPA axis response to stress. Certain data show that changes induced by chronic stress may be independent from the GCs levels, opening the possibility of existence of other poorly explored mechanisms and pathways through which stressors act. The hippocampal GABAergic parvalbumin-positive (PV+) interneurons represent an especially vulnerable population of neurons in chronic stress, which may be of key importance in the development of mood disorders. However, cellular and molecular hippocampal changes that arise as a consequence of chronic stress still represent a large and unexplored area. This review discusses the current knowledge about the PV+ interneurons of the hippocampus and the influence of chronic stress on this intriguing population of neurons.",
journal = "Reviews in the Neurosciences",
title = "Chronic stress, hippocampus and parvalbumin-positive interneurons: what do we know so far?",
volume = "27",
number = "4",
pages = "397-409",
doi = "10.1515/revneuro-2015-0042"
}
Zaletel, I., Filipović, D.,& Puškaš, N.. (2016). Chronic stress, hippocampus and parvalbumin-positive interneurons: what do we know so far?. in Reviews in the Neurosciences, 27(4), 397-409.
https://doi.org/10.1515/revneuro-2015-0042
Zaletel I, Filipović D, Puškaš N. Chronic stress, hippocampus and parvalbumin-positive interneurons: what do we know so far?. in Reviews in the Neurosciences. 2016;27(4):397-409.
doi:10.1515/revneuro-2015-0042 .
Zaletel, Ivan, Filipović, Dragana, Puškaš, Nela, "Chronic stress, hippocampus and parvalbumin-positive interneurons: what do we know so far?" in Reviews in the Neurosciences, 27, no. 4 (2016):397-409,
https://doi.org/10.1515/revneuro-2015-0042 . .
36
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33

Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus

Martinović, Jelena; Bernardi, Rick E.; Filipović, Dragana

(2014)

TY  - JOUR
AU  - Martinović, Jelena
AU  - Bernardi, Rick E.
AU  - Filipović, Dragana
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5826
AB  - Stress-related glucocorticoids and glutamate release has been implicated in depression. Glutamate neurotoxicity is mediated, in part, by the production of nitric oxide via nitric oxide synthase (NOS) isoforms and mitochondrial damage. We previously reported that chronic social isolation stress triggers proapoptotic signaling in the rat prefrontal cortex, but not in the hippocampus. Given that the hippocampus is highly sensitive to stress, we examined signaling cascades underlying the hippocampal cellular protection through the NOS pathway, antioxidant capacity and heat shock protein (Hsp) expression. We investigated neuronal (nNOS) and inducible (iNOS) protein levels, subcellular protein distributions of nuclear factor-kappa B (NF-kappa B), CuZnSOD and MnSOD activity, reduced glutathione (GSH), stress-inducible Hsp70 (Hsp70i) protein expression and serum corticosterone (CORT) levels of rats exposed to 21 days of chronic social isolation, an animal model of depression, alone or in combination with 2 h of acute immobilization or cold stress (combined stress). Both acute stressors elevated CORT, with lesser magnitude increase in chronically isolated rats exposed to novel acute stress as compared to acute stressors alone, indicating compromised HPA axis activity. Acute cold decreased nuclear CuZnSOD activity and stimulated NF-kappa B nuclear translocation. Chronic social isolation resulted in no activation of NF-kappa B, but led to decreased GSH, iNOS and increased nNOS and Hsp70i levels, alterations that remained following combined stressors. Decreased mitochondrial MnSOD activity after combined stressors suggests compromised detoxifying capacity. These data indicate that Hsp70i upregulation may provide hippocampal cellular protection against chronic social isolation stress mediated by downregulation of iNOS protein expression through suppression of NF-kappa B activation.
T2  - Journal of Neural Transmission
T1  - Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus
VL  - 121
IS  - 1
SP  - 3
EP  - 14
DO  - 10.1007/s00702-013-1066-1
ER  - 
@article{
author = "Martinović, Jelena and Bernardi, Rick E. and Filipović, Dragana",
year = "2014",
abstract = "Stress-related glucocorticoids and glutamate release has been implicated in depression. Glutamate neurotoxicity is mediated, in part, by the production of nitric oxide via nitric oxide synthase (NOS) isoforms and mitochondrial damage. We previously reported that chronic social isolation stress triggers proapoptotic signaling in the rat prefrontal cortex, but not in the hippocampus. Given that the hippocampus is highly sensitive to stress, we examined signaling cascades underlying the hippocampal cellular protection through the NOS pathway, antioxidant capacity and heat shock protein (Hsp) expression. We investigated neuronal (nNOS) and inducible (iNOS) protein levels, subcellular protein distributions of nuclear factor-kappa B (NF-kappa B), CuZnSOD and MnSOD activity, reduced glutathione (GSH), stress-inducible Hsp70 (Hsp70i) protein expression and serum corticosterone (CORT) levels of rats exposed to 21 days of chronic social isolation, an animal model of depression, alone or in combination with 2 h of acute immobilization or cold stress (combined stress). Both acute stressors elevated CORT, with lesser magnitude increase in chronically isolated rats exposed to novel acute stress as compared to acute stressors alone, indicating compromised HPA axis activity. Acute cold decreased nuclear CuZnSOD activity and stimulated NF-kappa B nuclear translocation. Chronic social isolation resulted in no activation of NF-kappa B, but led to decreased GSH, iNOS and increased nNOS and Hsp70i levels, alterations that remained following combined stressors. Decreased mitochondrial MnSOD activity after combined stressors suggests compromised detoxifying capacity. These data indicate that Hsp70i upregulation may provide hippocampal cellular protection against chronic social isolation stress mediated by downregulation of iNOS protein expression through suppression of NF-kappa B activation.",
journal = "Journal of Neural Transmission",
title = "Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus",
volume = "121",
number = "1",
pages = "3-14",
doi = "10.1007/s00702-013-1066-1"
}
Martinović, J., Bernardi, R. E.,& Filipović, D.. (2014). Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus. in Journal of Neural Transmission, 121(1), 3-14.
https://doi.org/10.1007/s00702-013-1066-1
Martinović J, Bernardi RE, Filipović D. Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus. in Journal of Neural Transmission. 2014;121(1):3-14.
doi:10.1007/s00702-013-1066-1 .
Martinović, Jelena, Bernardi, Rick E., Filipović, Dragana, "Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus" in Journal of Neural Transmission, 121, no. 1 (2014):3-14,
https://doi.org/10.1007/s00702-013-1066-1 . .
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Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: A histopathological study

Martinović, Jelena; Todorović, Nevena; Tomanović, Nada; Bošković, Maja; Djordjevic, Snezana; Lazarević-Pašti, Tamara; Bernardi, Rick E.; Đurđević, Aleksandra; Filipović, Dragana

(2014)

TY  - JOUR
AU  - Martinović, Jelena
AU  - Todorović, Nevena
AU  - Tomanović, Nada
AU  - Bošković, Maja
AU  - Djordjevic, Snezana
AU  - Lazarević-Pašti, Tamara
AU  - Bernardi, Rick E.
AU  - Đurđević, Aleksandra
AU  - Filipović, Dragana
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/6043
AB  - Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15 mg/kg/day) or clozapine (20 mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21 days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-kappa B (NF-kappa B), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-kappa B activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups resulted in liver injury. These data suggest that clozapine appears to have a higher potential to induce liver toxicity than fluoxetine. (C) 2014 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmaceutical Sciences
T1  - Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: A histopathological study
VL  - 59
SP  - 20
EP  - 30
DO  - 10.1016/j.ejps.2014.04.010
ER  - 
@article{
author = "Martinović, Jelena and Todorović, Nevena and Tomanović, Nada and Bošković, Maja and Djordjevic, Snezana and Lazarević-Pašti, Tamara and Bernardi, Rick E. and Đurđević, Aleksandra and Filipović, Dragana",
year = "2014",
abstract = "Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15 mg/kg/day) or clozapine (20 mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21 days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-kappa B (NF-kappa B), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-kappa B activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups resulted in liver injury. These data suggest that clozapine appears to have a higher potential to induce liver toxicity than fluoxetine. (C) 2014 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmaceutical Sciences",
title = "Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: A histopathological study",
volume = "59",
pages = "20-30",
doi = "10.1016/j.ejps.2014.04.010"
}
Martinović, J., Todorović, N., Tomanović, N., Bošković, M., Djordjevic, S., Lazarević-Pašti, T., Bernardi, R. E., Đurđević, A.,& Filipović, D.. (2014). Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: A histopathological study. in European Journal of Pharmaceutical Sciences, 59, 20-30.
https://doi.org/10.1016/j.ejps.2014.04.010
Martinović J, Todorović N, Tomanović N, Bošković M, Djordjevic S, Lazarević-Pašti T, Bernardi RE, Đurđević A, Filipović D. Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: A histopathological study. in European Journal of Pharmaceutical Sciences. 2014;59:20-30.
doi:10.1016/j.ejps.2014.04.010 .
Martinović, Jelena, Todorović, Nevena, Tomanović, Nada, Bošković, Maja, Djordjevic, Snezana, Lazarević-Pašti, Tamara, Bernardi, Rick E., Đurđević, Aleksandra, Filipović, Dragana, "Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: A histopathological study" in European Journal of Pharmaceutical Sciences, 59 (2014):20-30,
https://doi.org/10.1016/j.ejps.2014.04.010 . .
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