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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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