Molecular mechanisms of cellular responses on pathological changes in central neuronal system and peripheral organs of mammals

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Molecular mechanisms of cellular responses on pathological changes in central neuronal system and peripheral organs of mammals (en)
Молекуларни механизми патофизиолошких промена у ћелијама централног нервног система и периферног ткива код сисара (sr)
Molekularni mehanizmi patofizioloških promena u ćelijama centralnog nervnog sistema i perifernog tkiva kod sisara (sr_RS)
Authors

Publications

Progesterone Protects Prefrontal Cortex in Rat Model of Permanent Bilateral Common Carotid Occlusion via Progesterone Receptors and Akt/Erk/eNOS

Stanojlović, Miloš R.; Guševac Stojanović, Ivana; Zarić, Marina; Martinović, Jelena; Mitrović, Nataša Lj.; Grković, Ivana; Drakulić, Dunja R.

(2020)

TY  - JOUR
AU  - Stanojlović, Miloš R.
AU  - Guševac Stojanović, Ivana
AU  - Zarić, Marina
AU  - Martinović, Jelena
AU  - Mitrović, Nataša Lj.
AU  - Grković, Ivana
AU  - Drakulić, Dunja R.
PY  - 2020
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/8742
AB  - Sustained activation of pro-apoptotic signaling due to a sudden and prolonged disturbance of cerebral blood circulation governs the neurodegenerative processes in prefrontal cortex (PFC) of rats whose common carotid arteries are permanently occluded. The adequate neuroprotective therapy should minimize the activation of toxicity pathways and increase the activity of endogenous protective mechanisms. Several neuroprotectants have been proposed, including progesterone (P4). However, the underlying mechanism of its action in PFC following permanent bilateral occlusion of common carotid arteries is not completely investigated. We, thus herein, tested the impact of post-ischemic P4 treatment (1.7 mg/kg for seven consecutive days) on previously reported aberrant neuronal morphology and amount of DNA fragmentation, as well as the expression of progesterone receptors along with the key elements of Akt/Erk/eNOS signal transduction pathway (Bax, Bcl-2, cytochrome C, caspase 3, PARP, and the level of nitric oxide). The obtained results indicate that potential amelioration of histological changes in PFC might be associated with the absence of activation of Bax/caspase 3 signaling cascade and the decline of DNA fragmentation. The study also provides the evidence that P4 treatment in repeated regiment of administration might be effective in neuronal protection against ischemic insult due to re-establishment of the compromised action of Akt/Erk/eNOS-mediated signaling pathway and the upregulation of progesterone receptors. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
T2  - Cellular and Molecular Neurobiology
T1  - Progesterone Protects Prefrontal Cortex in Rat Model of Permanent Bilateral Common Carotid Occlusion via Progesterone Receptors and Akt/Erk/eNOS
VL  - 40
IS  - 5
SP  - 829
EP  - 843
DO  - 10.1007/s10571-019-00777-2
ER  - 
@article{
author = "Stanojlović, Miloš R. and Guševac Stojanović, Ivana and Zarić, Marina and Martinović, Jelena and Mitrović, Nataša Lj. and Grković, Ivana and Drakulić, Dunja R.",
year = "2020",
abstract = "Sustained activation of pro-apoptotic signaling due to a sudden and prolonged disturbance of cerebral blood circulation governs the neurodegenerative processes in prefrontal cortex (PFC) of rats whose common carotid arteries are permanently occluded. The adequate neuroprotective therapy should minimize the activation of toxicity pathways and increase the activity of endogenous protective mechanisms. Several neuroprotectants have been proposed, including progesterone (P4). However, the underlying mechanism of its action in PFC following permanent bilateral occlusion of common carotid arteries is not completely investigated. We, thus herein, tested the impact of post-ischemic P4 treatment (1.7 mg/kg for seven consecutive days) on previously reported aberrant neuronal morphology and amount of DNA fragmentation, as well as the expression of progesterone receptors along with the key elements of Akt/Erk/eNOS signal transduction pathway (Bax, Bcl-2, cytochrome C, caspase 3, PARP, and the level of nitric oxide). The obtained results indicate that potential amelioration of histological changes in PFC might be associated with the absence of activation of Bax/caspase 3 signaling cascade and the decline of DNA fragmentation. The study also provides the evidence that P4 treatment in repeated regiment of administration might be effective in neuronal protection against ischemic insult due to re-establishment of the compromised action of Akt/Erk/eNOS-mediated signaling pathway and the upregulation of progesterone receptors. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.",
journal = "Cellular and Molecular Neurobiology",
title = "Progesterone Protects Prefrontal Cortex in Rat Model of Permanent Bilateral Common Carotid Occlusion via Progesterone Receptors and Akt/Erk/eNOS",
volume = "40",
number = "5",
pages = "829-843",
doi = "10.1007/s10571-019-00777-2"
}
Stanojlović, M. R., Guševac Stojanović, I., Zarić, M., Martinović, J., Mitrović, N. Lj., Grković, I.,& Drakulić, D. R.. (2020). Progesterone Protects Prefrontal Cortex in Rat Model of Permanent Bilateral Common Carotid Occlusion via Progesterone Receptors and Akt/Erk/eNOS. in Cellular and Molecular Neurobiology, 40(5), 829-843.
https://doi.org/10.1007/s10571-019-00777-2
Stanojlović MR, Guševac Stojanović I, Zarić M, Martinović J, Mitrović NL, Grković I, Drakulić DR. Progesterone Protects Prefrontal Cortex in Rat Model of Permanent Bilateral Common Carotid Occlusion via Progesterone Receptors and Akt/Erk/eNOS. in Cellular and Molecular Neurobiology. 2020;40(5):829-843.
doi:10.1007/s10571-019-00777-2 .
Stanojlović, Miloš R., Guševac Stojanović, Ivana, Zarić, Marina, Martinović, Jelena, Mitrović, Nataša Lj., Grković, Ivana, Drakulić, Dunja R., "Progesterone Protects Prefrontal Cortex in Rat Model of Permanent Bilateral Common Carotid Occlusion via Progesterone Receptors and Akt/Erk/eNOS" in Cellular and Molecular Neurobiology, 40, no. 5 (2020):829-843,
https://doi.org/10.1007/s10571-019-00777-2 . .
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Estradiol induces synaptic rearrangements

Grković, Ivana; Mitrović, Nataša Lj.

(2020)

TY  - CHAP
AU  - Grković, Ivana
AU  - Mitrović, Nataša Lj.
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9056
AB  - 17β-Estradiol (E2) is a potent steroid hormone of both gonadal and neuronal origin that exerts profound effects on neuroplasticity in several brain regions. Dendritic spine and synapse formation and rearrangements are modulated and mediated by estrogens. In this chapter, we highlighted the essential background concerning the effects of E2 on synaptic rearrangements accompanied by synaptic plasticity in E2-sensitive brain regions that mediate learning and memory, i.e., cortex and hippocampus. We also address details of the molecular mechanisms underlying E2 regulation of spine dynamics. The proposed models of action of E2 overlaps with that for well-established synaptic modulators, such as adenosine. Thus, the possible synergistic effects of those two molecules in respect to synaptic rearrangement and plasticity were presented.
T2  - Vitamins and Hormons
T1  - Estradiol induces synaptic rearrangements
VL  - 114
SP  - 233
EP  - 256
DO  - 10.1016/bs.vh.2020.04.006
ER  - 
@inbook{
author = "Grković, Ivana and Mitrović, Nataša Lj.",
year = "2020",
abstract = "17β-Estradiol (E2) is a potent steroid hormone of both gonadal and neuronal origin that exerts profound effects on neuroplasticity in several brain regions. Dendritic spine and synapse formation and rearrangements are modulated and mediated by estrogens. In this chapter, we highlighted the essential background concerning the effects of E2 on synaptic rearrangements accompanied by synaptic plasticity in E2-sensitive brain regions that mediate learning and memory, i.e., cortex and hippocampus. We also address details of the molecular mechanisms underlying E2 regulation of spine dynamics. The proposed models of action of E2 overlaps with that for well-established synaptic modulators, such as adenosine. Thus, the possible synergistic effects of those two molecules in respect to synaptic rearrangement and plasticity were presented.",
journal = "Vitamins and Hormons",
booktitle = "Estradiol induces synaptic rearrangements",
volume = "114",
pages = "233-256",
doi = "10.1016/bs.vh.2020.04.006"
}
Grković, I.,& Mitrović, N. Lj.. (2020). Estradiol induces synaptic rearrangements. in Vitamins and Hormons, 114, 233-256.
https://doi.org/10.1016/bs.vh.2020.04.006
Grković I, Mitrović NL. Estradiol induces synaptic rearrangements. in Vitamins and Hormons. 2020;114:233-256.
doi:10.1016/bs.vh.2020.04.006 .
Grković, Ivana, Mitrović, Nataša Lj., "Estradiol induces synaptic rearrangements" in Vitamins and Hormons, 114 (2020):233-256,
https://doi.org/10.1016/bs.vh.2020.04.006 . .
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Antioxidant status and clinicopathological parameters in patients with Parkinson's disease

Miletić Vukajlović, Jadranka; Pejić, Snežana; Todorović, Ana; Valenta-Šobot, Ana; Drakulić, Dunja R.; Pavlović, Ivan; Stefanović, Aleksandra; Prostran, Milica; Ilić, Tihomir V.; Stojanov, Marina

(2019)

TY  - JOUR
AU  - Miletić Vukajlović, Jadranka
AU  - Pejić, Snežana
AU  - Todorović, Ana
AU  - Valenta-Šobot, Ana
AU  - Drakulić, Dunja R.
AU  - Pavlović, Ivan
AU  - Stefanović, Aleksandra
AU  - Prostran, Milica
AU  - Ilić, Tihomir V.
AU  - Stojanov, Marina
PY  - 2019
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/8407
AB  - Backgroun / Aim. Constant production of free radicals and antioxidants (AO) in the cell is a part of normal cellular function. Their imbalance might take a part in pathophysiology of many diseases, including Parkinson’s disease (PD). Evaluation of the disease status, prooxidant-antioxidant balance (PAB) and antioxidants are being widely estimated. The aim of this study was to examine potential interaction between several AO variables (GSH, SOD, CAT and PAB) and clinicopathological features of patients with PD, particularly Hoehn and Yahr (H&Y) stage. Methods. A multivariate analysis of variance (MANOVA) was conducted to test the hypothesis of the mean differences between clinicopathological characteristics (gender, age at examination, duration of the disease, and H&Y stage) and AO variables, compared with age/sex matched healthy controls. The study included 91 patients with idiopatic PD patients and 20 healthy controls. Results. The multivariate effect size was estimated at 0.269, p <0.001, implying that 27.0% of the variance of the dependent variables was accounted for H&Y stage. Univariate tests showed that there were significant differences (p <0.001) across the H&Y stage on all AO variables. The H&Y stage remained significant predictor after controlling for the second variable, the disease duration (p <0.001, η2 = 0.249), and there were still significant differences across the H&Y stage on all variables, with effect size ( η2) ranging from 0.132, p =0.011 (lnGSH) to the still high values of 0.535 (lnPAB), 0.627 (lnSOD) and 0.964 (lnCAT). Conclusion. The results indicate that higher level of oxidative stress in blood of PD patients is possibly related to PD stage. Along with reduction of SOD and GSH level, CAT activity was elevated in comparison to healthy subjects. Furthermore, Pwas shifted toward oxidative stress.
T2  - Vojnosanitetski pregled
T1  - Antioxidant status and clinicopathological parameters in patients with Parkinson's disease
VL  - 77
IS  - 7
SP  - 724
EP  - 730
DO  - 10.2298/VSP180718148M
ER  - 
@article{
author = "Miletić Vukajlović, Jadranka and Pejić, Snežana and Todorović, Ana and Valenta-Šobot, Ana and Drakulić, Dunja R. and Pavlović, Ivan and Stefanović, Aleksandra and Prostran, Milica and Ilić, Tihomir V. and Stojanov, Marina",
year = "2019",
abstract = "Backgroun / Aim. Constant production of free radicals and antioxidants (AO) in the cell is a part of normal cellular function. Their imbalance might take a part in pathophysiology of many diseases, including Parkinson’s disease (PD). Evaluation of the disease status, prooxidant-antioxidant balance (PAB) and antioxidants are being widely estimated. The aim of this study was to examine potential interaction between several AO variables (GSH, SOD, CAT and PAB) and clinicopathological features of patients with PD, particularly Hoehn and Yahr (H&Y) stage. Methods. A multivariate analysis of variance (MANOVA) was conducted to test the hypothesis of the mean differences between clinicopathological characteristics (gender, age at examination, duration of the disease, and H&Y stage) and AO variables, compared with age/sex matched healthy controls. The study included 91 patients with idiopatic PD patients and 20 healthy controls. Results. The multivariate effect size was estimated at 0.269, p <0.001, implying that 27.0% of the variance of the dependent variables was accounted for H&Y stage. Univariate tests showed that there were significant differences (p <0.001) across the H&Y stage on all AO variables. The H&Y stage remained significant predictor after controlling for the second variable, the disease duration (p <0.001, η2 = 0.249), and there were still significant differences across the H&Y stage on all variables, with effect size ( η2) ranging from 0.132, p =0.011 (lnGSH) to the still high values of 0.535 (lnPAB), 0.627 (lnSOD) and 0.964 (lnCAT). Conclusion. The results indicate that higher level of oxidative stress in blood of PD patients is possibly related to PD stage. Along with reduction of SOD and GSH level, CAT activity was elevated in comparison to healthy subjects. Furthermore, Pwas shifted toward oxidative stress.",
journal = "Vojnosanitetski pregled",
title = "Antioxidant status and clinicopathological parameters in patients with Parkinson's disease",
volume = "77",
number = "7",
pages = "724-730",
doi = "10.2298/VSP180718148M"
}
Miletić Vukajlović, J., Pejić, S., Todorović, A., Valenta-Šobot, A., Drakulić, D. R., Pavlović, I., Stefanović, A., Prostran, M., Ilić, T. V.,& Stojanov, M.. (2019). Antioxidant status and clinicopathological parameters in patients with Parkinson's disease. in Vojnosanitetski pregled, 77(7), 724-730.
https://doi.org/10.2298/VSP180718148M
Miletić Vukajlović J, Pejić S, Todorović A, Valenta-Šobot A, Drakulić DR, Pavlović I, Stefanović A, Prostran M, Ilić TV, Stojanov M. Antioxidant status and clinicopathological parameters in patients with Parkinson's disease. in Vojnosanitetski pregled. 2019;77(7):724-730.
doi:10.2298/VSP180718148M .
Miletić Vukajlović, Jadranka, Pejić, Snežana, Todorović, Ana, Valenta-Šobot, Ana, Drakulić, Dunja R., Pavlović, Ivan, Stefanović, Aleksandra, Prostran, Milica, Ilić, Tihomir V., Stojanov, Marina, "Antioxidant status and clinicopathological parameters in patients with Parkinson's disease" in Vojnosanitetski pregled, 77, no. 7 (2019):724-730,
https://doi.org/10.2298/VSP180718148M . .
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1
1

Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression

Stefanović, Bojana; Spasojević, Nataša; Jovanović, Predrag; Dronjak, Slađana

(2019)

TY  - JOUR
AU  - Stefanović, Bojana
AU  - Spasojević, Nataša
AU  - Jovanović, Predrag
AU  - Dronjak, Slađana
PY  - 2019
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/8410
AB  - This study investigated the effects of melatonin treatment on adrenal catecholamine content, synthesis, uptake, and vesicular transport induced by the chronic unpredictable mild stress (CUMS) model of depression in rats. This entailed quantifying the norepinephrine, epinephrine, mRNA, and protein levels of tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), norepinephrine transporter (NET), and vesicular monoamine transporter 2 (VMAT2) in the adrenal medulla. CUMS caused a significant depletion of norepinephrine stores and protein levels of TH, DBH, and NET, whereas the gene expression of PNMT was increased. It was observed that melatonin treatment in the CUMS rats prevented the stress-induced decrease in norepinephrine content and the protein expression of TH, DBH, and NET in the adrenal medulla of chronically stressed rats. The present study demonstrates the stimulatory effect of melatonin on adrenomedullary synthesis, the uptake and content of catecholamine in the rat model of chronic stress-induced depression. © 2019, Published by NRC Research Press.
T2  - Canadian Journal of Physiology and Pharmacology
T1  - Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression
VL  - 97
IS  - 7
SP  - 685
EP  - 690
DO  - 10.1139/cjpp-2018-0612
ER  - 
@article{
author = "Stefanović, Bojana and Spasojević, Nataša and Jovanović, Predrag and Dronjak, Slađana",
year = "2019",
abstract = "This study investigated the effects of melatonin treatment on adrenal catecholamine content, synthesis, uptake, and vesicular transport induced by the chronic unpredictable mild stress (CUMS) model of depression in rats. This entailed quantifying the norepinephrine, epinephrine, mRNA, and protein levels of tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), norepinephrine transporter (NET), and vesicular monoamine transporter 2 (VMAT2) in the adrenal medulla. CUMS caused a significant depletion of norepinephrine stores and protein levels of TH, DBH, and NET, whereas the gene expression of PNMT was increased. It was observed that melatonin treatment in the CUMS rats prevented the stress-induced decrease in norepinephrine content and the protein expression of TH, DBH, and NET in the adrenal medulla of chronically stressed rats. The present study demonstrates the stimulatory effect of melatonin on adrenomedullary synthesis, the uptake and content of catecholamine in the rat model of chronic stress-induced depression. © 2019, Published by NRC Research Press.",
journal = "Canadian Journal of Physiology and Pharmacology",
title = "Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression",
volume = "97",
number = "7",
pages = "685-690",
doi = "10.1139/cjpp-2018-0612"
}
Stefanović, B., Spasojević, N., Jovanović, P.,& Dronjak, S.. (2019). Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression. in Canadian Journal of Physiology and Pharmacology, 97(7), 685-690.
https://doi.org/10.1139/cjpp-2018-0612
Stefanović B, Spasojević N, Jovanović P, Dronjak S. Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression. in Canadian Journal of Physiology and Pharmacology. 2019;97(7):685-690.
doi:10.1139/cjpp-2018-0612 .
Stefanović, Bojana, Spasojević, Nataša, Jovanović, Predrag, Dronjak, Slađana, "Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression" in Canadian Journal of Physiology and Pharmacology, 97, no. 7 (2019):685-690,
https://doi.org/10.1139/cjpp-2018-0612 . .
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6

Oxytocin modulates the expression of norepinephrine transporter, β3-adrenoceptors and muscarinic M2 receptors in the hearts of socially isolated rats

Jovanović, Predrag; Spasojević, Nataša; Puškaš, Nela; Stefanović, Bojana; Dronjak, Slađana

(2019)

TY  - JOUR
AU  - Jovanović, Predrag
AU  - Spasojević, Nataša
AU  - Puškaš, Nela
AU  - Stefanović, Bojana
AU  - Dronjak, Slađana
PY  - 2019
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/8400
AB  - Social stress produces behavioral alterations, and autonomic and cardiac dysfunction in animals. In addition to the well-known roles of oxytocin on birth and maternal bonding, recent evidence shows that this neuropeptide possesses cardio-protective properties. However less is known about its role in the regulation of the autonomic nervous system. The direct influence of oxytocin on the cardiac catecholamine synthesizing enzyme, transport beta-adrenoceptors and muscarinic receptors in animals exposed to chronic social isolation stress has not yet been studied. In this study, we examined the influence of peripheral chronic oxytocin treatment on anxiety-related behavior, the morphology and content of epinephrine and norepinephrine, mRNA and protein levels of tyrosine hydroxylase (TH), norepinephrine transporter (NET) and receptors <beta> 3 (β3-AR) and muscarinic 2 (M2 MR) in the right and left cardiac atrium and ventricle of chronically socially isolated male rats. Our results show that oxytocin treatment exhibits an anxiolytic effect, decreases the heart/body weight ratio and prevents the hypertrophy of cardiomyocytes in the wall of the left ventricle of stressed rats. Epinephrine and TH protein levels were unchanged after prolonged oxytocin treatment. Peripheral oxytocin administration led to the enhancement of gene expression of β3-AR in both atria, NET protein in the left ventricle and gene expression of M2 MR in the right atrium and the left ventricle of chronically socially isolated rats. The study provides evidence that oxytocin treatment in chronically socially isolated animals enhances norepinephrine uptake and expression of cardio-inhibitory receptors in cardiac tissues, which could have a beneficial effect on the cardiovascular system under the increased activity of the sympathoneural system. © 2018 Elsevier Inc.
T2  - Peptides
T1  - Oxytocin modulates the expression of norepinephrine transporter, β3-adrenoceptors and muscarinic M2 receptors in the hearts of socially isolated rats
VL  - 111
SP  - 132
EP  - 141
DO  - 10.1016/j.peptides.2018.06.008
ER  - 
@article{
author = "Jovanović, Predrag and Spasojević, Nataša and Puškaš, Nela and Stefanović, Bojana and Dronjak, Slađana",
year = "2019",
abstract = "Social stress produces behavioral alterations, and autonomic and cardiac dysfunction in animals. In addition to the well-known roles of oxytocin on birth and maternal bonding, recent evidence shows that this neuropeptide possesses cardio-protective properties. However less is known about its role in the regulation of the autonomic nervous system. The direct influence of oxytocin on the cardiac catecholamine synthesizing enzyme, transport beta-adrenoceptors and muscarinic receptors in animals exposed to chronic social isolation stress has not yet been studied. In this study, we examined the influence of peripheral chronic oxytocin treatment on anxiety-related behavior, the morphology and content of epinephrine and norepinephrine, mRNA and protein levels of tyrosine hydroxylase (TH), norepinephrine transporter (NET) and receptors <beta> 3 (β3-AR) and muscarinic 2 (M2 MR) in the right and left cardiac atrium and ventricle of chronically socially isolated male rats. Our results show that oxytocin treatment exhibits an anxiolytic effect, decreases the heart/body weight ratio and prevents the hypertrophy of cardiomyocytes in the wall of the left ventricle of stressed rats. Epinephrine and TH protein levels were unchanged after prolonged oxytocin treatment. Peripheral oxytocin administration led to the enhancement of gene expression of β3-AR in both atria, NET protein in the left ventricle and gene expression of M2 MR in the right atrium and the left ventricle of chronically socially isolated rats. The study provides evidence that oxytocin treatment in chronically socially isolated animals enhances norepinephrine uptake and expression of cardio-inhibitory receptors in cardiac tissues, which could have a beneficial effect on the cardiovascular system under the increased activity of the sympathoneural system. © 2018 Elsevier Inc.",
journal = "Peptides",
title = "Oxytocin modulates the expression of norepinephrine transporter, β3-adrenoceptors and muscarinic M2 receptors in the hearts of socially isolated rats",
volume = "111",
pages = "132-141",
doi = "10.1016/j.peptides.2018.06.008"
}
Jovanović, P., Spasojević, N., Puškaš, N., Stefanović, B.,& Dronjak, S.. (2019). Oxytocin modulates the expression of norepinephrine transporter, β3-adrenoceptors and muscarinic M2 receptors in the hearts of socially isolated rats. in Peptides, 111, 132-141.
https://doi.org/10.1016/j.peptides.2018.06.008
Jovanović P, Spasojević N, Puškaš N, Stefanović B, Dronjak S. Oxytocin modulates the expression of norepinephrine transporter, β3-adrenoceptors and muscarinic M2 receptors in the hearts of socially isolated rats. in Peptides. 2019;111:132-141.
doi:10.1016/j.peptides.2018.06.008 .
Jovanović, Predrag, Spasojević, Nataša, Puškaš, Nela, Stefanović, Bojana, Dronjak, Slađana, "Oxytocin modulates the expression of norepinephrine transporter, β3-adrenoceptors and muscarinic M2 receptors in the hearts of socially isolated rats" in Peptides, 111 (2019):132-141,
https://doi.org/10.1016/j.peptides.2018.06.008 . .
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Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression

Stefanović, Bojana; Spasojević, Nataša; Jovanović, Predrag; Dronjak, Slađana

(2019)

TY  - JOUR
AU  - Stefanović, Bojana
AU  - Spasojević, Nataša
AU  - Jovanović, Predrag
AU  - Dronjak, Slađana
PY  - 2019
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/8361
AB  - This study investigated the effects of melatonin treatment on adrenal catecholamine content, synthesis, uptake, and vesicular transport induced by the chronic unpredictable mild stress (CUMS) model of depression in rats. This entailed quantifying the norepinephrine, epinephrine, mRNA, and protein levels of tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), norepinephrine transporter (NET), and vesicular monoamine transporter 2 (VMAT2) in the adrenal medulla. CUMS caused a significant depletion of norepinephrine stores and protein levels of TH, DBH, and NET, whereas the gene expression of PNMT was increased. It was observed that melatonin treatment in the CUMS rats prevented the stress-induced decrease in norepinephrine content and the protein expression of TH, DBH, and NET in the adrenal medulla of chronically stressed rats. The present study demonstrates the stimulatory effect of melatonin on adrenomedullary synthesis, the uptake and content of catecholamine in the rat model of chronic stress-induced depression. © 2019, Published by NRC Research Press.
T2  - Canadian Journal of Physiology and Pharmacology
T1  - Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression
VL  - 97
IS  - 7
SP  - 685
EP  - 690
DO  - 10.1139/cjpp-2018-0612
ER  - 
@article{
author = "Stefanović, Bojana and Spasojević, Nataša and Jovanović, Predrag and Dronjak, Slađana",
year = "2019",
abstract = "This study investigated the effects of melatonin treatment on adrenal catecholamine content, synthesis, uptake, and vesicular transport induced by the chronic unpredictable mild stress (CUMS) model of depression in rats. This entailed quantifying the norepinephrine, epinephrine, mRNA, and protein levels of tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), norepinephrine transporter (NET), and vesicular monoamine transporter 2 (VMAT2) in the adrenal medulla. CUMS caused a significant depletion of norepinephrine stores and protein levels of TH, DBH, and NET, whereas the gene expression of PNMT was increased. It was observed that melatonin treatment in the CUMS rats prevented the stress-induced decrease in norepinephrine content and the protein expression of TH, DBH, and NET in the adrenal medulla of chronically stressed rats. The present study demonstrates the stimulatory effect of melatonin on adrenomedullary synthesis, the uptake and content of catecholamine in the rat model of chronic stress-induced depression. © 2019, Published by NRC Research Press.",
journal = "Canadian Journal of Physiology and Pharmacology",
title = "Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression",
volume = "97",
number = "7",
pages = "685-690",
doi = "10.1139/cjpp-2018-0612"
}
Stefanović, B., Spasojević, N., Jovanović, P.,& Dronjak, S.. (2019). Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression. in Canadian Journal of Physiology and Pharmacology, 97(7), 685-690.
https://doi.org/10.1139/cjpp-2018-0612
Stefanović B, Spasojević N, Jovanović P, Dronjak S. Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression. in Canadian Journal of Physiology and Pharmacology. 2019;97(7):685-690.
doi:10.1139/cjpp-2018-0612 .
Stefanović, Bojana, Spasojević, Nataša, Jovanović, Predrag, Dronjak, Slađana, "Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression" in Canadian Journal of Physiology and Pharmacology, 97, no. 7 (2019):685-690,
https://doi.org/10.1139/cjpp-2018-0612 . .
8
8
6

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  - http://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 . .
5
5
5

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  - http://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 . .
11
10
10

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  - http://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 . .
13
12
12

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  - http://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 . .
9
8
7

Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement

Grković, Ivana; Mitrović, Nataša Lj.; Dragić, Milorad; Adžić, Marija; Drakulić, Dunja R.; Nedeljković, Nadežda

(2019)

TY  - JOUR
AU  - Grković, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Dragić, Milorad
AU  - Adžić, Marija
AU  - Drakulić, Dunja R.
AU  - Nedeljković, Nadežda
PY  - 2019
UR  - http://link.springer.com/10.1007/s12035-018-1217-3
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/8102
AB  - Purinergic signaling is the main synaptic and non-synaptic signaling system in brain. ATP acts as a fast excitatory transmitter, while adenosine sets a global inhibitory tone within hippocampal neuronal networks. ATP and adenosine are interconnected by ectonucleotidase enzymes, which convert ATP to adenosine. Existing data point to the converging roles of ovarian steroids and purinergic signaling in synapse formation and refinement and synapse activity in the hippocampus. Therefore, in the present study, we have used enzyme histochemistry and expression analysis to obtain data on spatial distribution and expression of ecto-enzymes NTPDase1, NTPDase2, and ecto-5-nucleotidase (eN) after removal of ovaries (OVX) and estradiol replacement (E2) in female rat hippocampus. The results show that target ectonucleotidases are predominantly localized in synapse-rich hippocampal layers. The most represented NTPDase in the hippocampal tissue is NTPDase2, being at the same time the mostly affected ectonucleotidase by OVX and E2. Specifically, OVX decreases the expression of NTPDase2 and eN, whereas E2 restores their expression to control level. Impact of OVX and E2 on ectonucleotidase expression was also examined in purified synaptosome (SYN) and gliosome (GLIO) fractions. Data reveal that SYN expresses NTPDase1 and NTPDase2, both of which are reduced following OVX and restored with E2. GLIO exhibits NTPDase2-mediated ATP hydrolysis, which falls in OVX, and recovers by E2. These changes in the activity occur without parallel changes in NTPDase2-protein abundance. The same holds for eN. The lack of correlation between NTPDase2 and eN activities and their respective protein abundances suggest a non-genomic mode of E2 action, which is studied further in primary astrocyte culture. Since ovarian steroids shape hippocampal synaptic networks and regulate ectonucleotidase activities, it is possible that cognitive deficits seen after ovary removal may arise from the loss of E2 modulatory actions on ectonucleotidase expression in the hippocampus.
T2  - Molecular Neurobiology
T2  - Molecular Neurobiology
T1  - Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement
VL  - 56
IS  - 3
SP  - 1933
EP  - 1945
DO  - 10.1007/s12035-018-1217-3
ER  - 
@article{
author = "Grković, Ivana and Mitrović, Nataša Lj. and Dragić, Milorad and Adžić, Marija and Drakulić, Dunja R. and Nedeljković, Nadežda",
year = "2019",
abstract = "Purinergic signaling is the main synaptic and non-synaptic signaling system in brain. ATP acts as a fast excitatory transmitter, while adenosine sets a global inhibitory tone within hippocampal neuronal networks. ATP and adenosine are interconnected by ectonucleotidase enzymes, which convert ATP to adenosine. Existing data point to the converging roles of ovarian steroids and purinergic signaling in synapse formation and refinement and synapse activity in the hippocampus. Therefore, in the present study, we have used enzyme histochemistry and expression analysis to obtain data on spatial distribution and expression of ecto-enzymes NTPDase1, NTPDase2, and ecto-5-nucleotidase (eN) after removal of ovaries (OVX) and estradiol replacement (E2) in female rat hippocampus. The results show that target ectonucleotidases are predominantly localized in synapse-rich hippocampal layers. The most represented NTPDase in the hippocampal tissue is NTPDase2, being at the same time the mostly affected ectonucleotidase by OVX and E2. Specifically, OVX decreases the expression of NTPDase2 and eN, whereas E2 restores their expression to control level. Impact of OVX and E2 on ectonucleotidase expression was also examined in purified synaptosome (SYN) and gliosome (GLIO) fractions. Data reveal that SYN expresses NTPDase1 and NTPDase2, both of which are reduced following OVX and restored with E2. GLIO exhibits NTPDase2-mediated ATP hydrolysis, which falls in OVX, and recovers by E2. These changes in the activity occur without parallel changes in NTPDase2-protein abundance. The same holds for eN. The lack of correlation between NTPDase2 and eN activities and their respective protein abundances suggest a non-genomic mode of E2 action, which is studied further in primary astrocyte culture. Since ovarian steroids shape hippocampal synaptic networks and regulate ectonucleotidase activities, it is possible that cognitive deficits seen after ovary removal may arise from the loss of E2 modulatory actions on ectonucleotidase expression in the hippocampus.",
journal = "Molecular Neurobiology, Molecular Neurobiology",
title = "Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement",
volume = "56",
number = "3",
pages = "1933-1945",
doi = "10.1007/s12035-018-1217-3"
}
Grković, I., Mitrović, N. Lj., Dragić, M., Adžić, M., Drakulić, D. R.,& Nedeljković, N.. (2019). Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement. in Molecular Neurobiology, 56(3), 1933-1945.
https://doi.org/10.1007/s12035-018-1217-3
Grković I, Mitrović NL, Dragić M, Adžić M, Drakulić DR, Nedeljković N. Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement. in Molecular Neurobiology. 2019;56(3):1933-1945.
doi:10.1007/s12035-018-1217-3 .
Grković, Ivana, Mitrović, Nataša Lj., Dragić, Milorad, Adžić, Marija, Drakulić, Dunja R., Nedeljković, Nadežda, "Spatial Distribution and Expression of Ectonucleotidases in Rat Hippocampus After Removal of Ovaries and Estradiol Replacement" in Molecular Neurobiology, 56, no. 3 (2019):1933-1945,
https://doi.org/10.1007/s12035-018-1217-3 . .
1
10
9
9

Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack

Zarić, Marina; Drakulić, Dunja R.; Dragić, Milorad; Guševac Stojanović, Ivana; Mitrović, Nataša Lj.; Grković, Ivana; Martinović, Jelena

(2019)

TY  - JOUR
AU  - Zarić, Marina
AU  - Drakulić, Dunja R.
AU  - Dragić, Milorad
AU  - Guševac Stojanović, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Grković, Ivana
AU  - Martinović, Jelena
PY  - 2019
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0306452219303227
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/8203
AB  - Transient ischemic attack (TIA) represents brief neurological dysfunction of vascular origin without detectable infarction. Despite major clinical relevance characterization of post-TIA molecular changes using appropriate experimental model is lacking and no therapeutic agent has been established yet. Neurosteroid dehydroepiandrosterone (DHEA) arose as one of the candidates for cerebral ischemia treatment but its effects on TIA-like condition remain unknown. Seeking an animal model applicable for investigation of molecular alterations in mild ischemic conditions such as TIA, 15-min bilateral common carotid artery occlusion with 24-h reperfusion was performed to induce ischemia/ reperfusion (I/R) injury in adult male Wistar rats. Additionally, effects of 4-h post-operative DHEA treatment (20 mg/kg) were investigated in physiological and I/R conditions in hippocampus (HIP) and prefrontal cortex (PFC). The study revealed absence of sensorimotor deficits, cerebral infarcts and neurodegeneration along with preserved HIP and PFC overall neuronal morphology and unaltered malondialdehyde and reduced glutathione level following I/R and/or DHEA treatment. I/R induced nitric oxide burst in HIP and PFC was accompanied with increased neuronal nitric oxide synthase protein level exclusively in HIP. DHEA had no effects in physiological conditions, while increase of Bax/Bcl2 ratio and dissipation of mitochondrial membrane potential in treated I/R group suggested DHEA-mediated exacerbation of post-ischemic changes that might lead to pro-apoptotic events in HIP. Interestingly, DHEA restored I/R-induced NO to the control level in PFC. Obtained results indicated that I/R may serve as an appropriate model for investigation of molecular changes and treatment outcome following mild ischemic conditions such as TIA. © 2019 Elsevier Ltd
T2  - Neuroscience
T1  - Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack
VL  - 410
SP  - 128
EP  - 139
DO  - 10.1016/j.neuroscience.2019.05.006
ER  - 
@article{
author = "Zarić, Marina and Drakulić, Dunja R. and Dragić, Milorad and Guševac Stojanović, Ivana and Mitrović, Nataša Lj. and Grković, Ivana and Martinović, Jelena",
year = "2019",
abstract = "Transient ischemic attack (TIA) represents brief neurological dysfunction of vascular origin without detectable infarction. Despite major clinical relevance characterization of post-TIA molecular changes using appropriate experimental model is lacking and no therapeutic agent has been established yet. Neurosteroid dehydroepiandrosterone (DHEA) arose as one of the candidates for cerebral ischemia treatment but its effects on TIA-like condition remain unknown. Seeking an animal model applicable for investigation of molecular alterations in mild ischemic conditions such as TIA, 15-min bilateral common carotid artery occlusion with 24-h reperfusion was performed to induce ischemia/ reperfusion (I/R) injury in adult male Wistar rats. Additionally, effects of 4-h post-operative DHEA treatment (20 mg/kg) were investigated in physiological and I/R conditions in hippocampus (HIP) and prefrontal cortex (PFC). The study revealed absence of sensorimotor deficits, cerebral infarcts and neurodegeneration along with preserved HIP and PFC overall neuronal morphology and unaltered malondialdehyde and reduced glutathione level following I/R and/or DHEA treatment. I/R induced nitric oxide burst in HIP and PFC was accompanied with increased neuronal nitric oxide synthase protein level exclusively in HIP. DHEA had no effects in physiological conditions, while increase of Bax/Bcl2 ratio and dissipation of mitochondrial membrane potential in treated I/R group suggested DHEA-mediated exacerbation of post-ischemic changes that might lead to pro-apoptotic events in HIP. Interestingly, DHEA restored I/R-induced NO to the control level in PFC. Obtained results indicated that I/R may serve as an appropriate model for investigation of molecular changes and treatment outcome following mild ischemic conditions such as TIA. © 2019 Elsevier Ltd",
journal = "Neuroscience",
title = "Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack",
volume = "410",
pages = "128-139",
doi = "10.1016/j.neuroscience.2019.05.006"
}
Zarić, M., Drakulić, D. R., Dragić, M., Guševac Stojanović, I., Mitrović, N. Lj., Grković, I.,& Martinović, J.. (2019). Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack. in Neuroscience, 410, 128-139.
https://doi.org/10.1016/j.neuroscience.2019.05.006
Zarić M, Drakulić DR, Dragić M, Guševac Stojanović I, Mitrović NL, Grković I, Martinović J. Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack. in Neuroscience. 2019;410:128-139.
doi:10.1016/j.neuroscience.2019.05.006 .
Zarić, Marina, Drakulić, Dunja R., Dragić, Milorad, Guševac Stojanović, Ivana, Mitrović, Nataša Lj., Grković, Ivana, Martinović, Jelena, "Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack" in Neuroscience, 410 (2019):128-139,
https://doi.org/10.1016/j.neuroscience.2019.05.006 . .
1
1
1

Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats

Mitrović, Nataša Lj.; Dragić, Milorad; Zarić, Marina; Drakulić, Dunja R.; Nedeljković, Nadežda; Grković, Ivana

(2019)

TY  - JOUR
AU  - Mitrović, Nataša Lj.
AU  - Dragić, Milorad
AU  - Zarić, Marina
AU  - Drakulić, Dunja R.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2019
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/8497
AB  - Extracellular adenine nucleotides and nucleosides, such as adenosine-5'-triphosphate (ATP) and adenosine, are among least investigated signaling factors that participate in 17β-estradiol (E2)-mediated synaptic rearrangements in rodent hippocampus. Their levels in the extrasynaptic space are tightly controlled by ecto-nucleoside triphosphate diphosphohydrolases1-3 (NTPDase1-3)/ecto-5'-nucleotidase (eN) enzyme chain. Therefore, the aim of the present study was to get closer insight in the E2-induced decrease in NTPDase and eN activity in the hippocampal synaptic compartment of male rats and to identify estradiol receptors (ERs i.e. ERα, ERβ or GPER1) responsible for the observed effects of E2. In this study we show indiscriminate participation of estradiol receptor α (ERα), -β (ERβ) and G- protein coupled estrogen receptor 1 (GPER1) in the mediation of E2 actions in hippocampal synaptosomes of male rats. Synaptic NTPDase1-3 activities are modulated only through activation of ERβ, while activation of ERα, -β and/or non-classical GPER1 decreases synaptic eN activity. Since both ATP and adenosine function as neuromodulators in the hippocampal networks, influencing its function, profound knowledge of mechanisms by which ectonucleotidases are regulated/modulated is of great importance. © 2019 Elsevier B.V.
T2  - Neuroscience Letters
T1  - Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats
VL  - 712
SP  - 134474
DO  - 10.1016/j.neulet.2019.134474
ER  - 
@article{
author = "Mitrović, Nataša Lj. and Dragić, Milorad and Zarić, Marina and Drakulić, Dunja R. and Nedeljković, Nadežda and Grković, Ivana",
year = "2019",
abstract = "Extracellular adenine nucleotides and nucleosides, such as adenosine-5'-triphosphate (ATP) and adenosine, are among least investigated signaling factors that participate in 17β-estradiol (E2)-mediated synaptic rearrangements in rodent hippocampus. Their levels in the extrasynaptic space are tightly controlled by ecto-nucleoside triphosphate diphosphohydrolases1-3 (NTPDase1-3)/ecto-5'-nucleotidase (eN) enzyme chain. Therefore, the aim of the present study was to get closer insight in the E2-induced decrease in NTPDase and eN activity in the hippocampal synaptic compartment of male rats and to identify estradiol receptors (ERs i.e. ERα, ERβ or GPER1) responsible for the observed effects of E2. In this study we show indiscriminate participation of estradiol receptor α (ERα), -β (ERβ) and G- protein coupled estrogen receptor 1 (GPER1) in the mediation of E2 actions in hippocampal synaptosomes of male rats. Synaptic NTPDase1-3 activities are modulated only through activation of ERβ, while activation of ERα, -β and/or non-classical GPER1 decreases synaptic eN activity. Since both ATP and adenosine function as neuromodulators in the hippocampal networks, influencing its function, profound knowledge of mechanisms by which ectonucleotidases are regulated/modulated is of great importance. © 2019 Elsevier B.V.",
journal = "Neuroscience Letters",
title = "Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats",
volume = "712",
pages = "134474",
doi = "10.1016/j.neulet.2019.134474"
}
Mitrović, N. Lj., Dragić, M., Zarić, M., Drakulić, D. R., Nedeljković, N.,& Grković, I.. (2019). Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats. in Neuroscience Letters, 712, 134474.
https://doi.org/10.1016/j.neulet.2019.134474
Mitrović NL, Dragić M, Zarić M, Drakulić DR, Nedeljković N, Grković I. Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats. in Neuroscience Letters. 2019;712:134474.
doi:10.1016/j.neulet.2019.134474 .
Mitrović, Nataša Lj., Dragić, Milorad, Zarić, Marina, Drakulić, Dunja R., Nedeljković, Nadežda, Grković, Ivana, "Estrogen receptors modulate ectonucleotidases activity in hippocampal synaptosomes of male rats" in Neuroscience Letters, 712 (2019):134474,
https://doi.org/10.1016/j.neulet.2019.134474 . .
2
1
2

Efekat kratkotrajne moždane ishemije/reperfuzije i tretmana dehidroepiandrosteronom na komponente signalnog puta NMDA receptora u hipokampusu i prečeonoj kori pacova

Zarić, Marina

(Универзитет у Београду, Биолошки факултет, 2019)

TY  - THES
AU  - Zarić, Marina
PY  - 2019
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7338
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:21574/bdef:Content/download
UR  - https://plus.sr.cobiss.net/opac7/bib/1025242546
UR  - http://nardus.mpn.gov.rs/123456789/12179
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/8507
AB  - Stanje moždane ishemije/reperfuzije (I/R) karakteristično je za cerebrovaskularnaoboljenja kao što su moţdani udar i tranzitorni ishemijski atak(TIA). Promena signalizacije posredovana N-metil-D-aspartat (NMDA)receptorom ima značajnu ulogu u I/R-uzrokovanom oštećenju, dok jedehidroepiandrosteron (DHEA), pozitvni alosterični modulator NMDAreceptora, najčešće okarakterisan kao neuroprotektivan u tretmanu ishemičnihstanja.U ovoj disertaciji ispitivana je proteinska ekspresija komponentikompleksa NMDA receptora i njegove nishodne signalizacije u hipokampusu iprečeonoj kori muţjaka pacova Wistar soja 24 sata nakon podvezivanja obezajedničke karotidne arterije u trajanju od 15 min i/ili efekat tretmana DHEAprimenjenog 4 sata od hirurške procedure. Praćenje senzo-motorne funkcije iprisustvo infarktnih lezija na presecima celog mozga korišćeno je za validacijuI/R modela za proučavanje blaţih ishemičnih stanja poput TIA. Takođe,izvršeno je ispitivanje efekata I/R i tretmana na histo/morfološkom nivou.Odsustvo senzo-motornih deficita i infarktnih lezija kao i očuvanastruktura tkiva i morfologija neurona u hipokampusu i prečeonoj kori nakonI/R ukazuju na potencijalnu primenu modela u ispitivanju umerenihishemičnih stanja. Region-specifične promene signalnog puta NMDAreceptor/neuralna azot oksid sintaza/azot oksid nakon kratkotrajne I/R govoreu prilog većoj osetljivosti hipokampusa u odnosu na prečeonu koru. EfekatDHEA uočen je isključivo nakon I/R, vraćajući u prečeonoj kori parametare nakontrolnu vrednost, dok u hipokampusu promene Bax/Bcl -2 odnosa ipotencijala mitohondrijske membrane ukazuju na pokretanje pro-apoptotskihdešavanja. Stoga, prethodno okarakterisani neuroprotektivni efekat DHEAtreba dodatno istraţiti.
AB  - Cerebral ischemia/reperfusion (I/R) is characteristic of cerebro-vasculardiseases such as stroke and transient ischemic attack (TIA). Alterations of Nmethyl-D-aspartate (NMDA) receptor-mediated signalling pathway are wellrecognized features of I/R-governed damage, while dehydroepiandrosterone(DHEA), its positive allosteric modulator, has been previously described asneuroprotective and potentially promising for therapy of ischemic conditions.In this doctoral dissertation changes of components of the NMDAreceptor complex and downstream signalling in hippocampus and prefrontalcortex were examined in male Wistar rats 24 h following 15 min bilateralcommon carotid artery occlusion. In addition, effects of 4 h post-surgical DHEAtreatment were investigated. Sensory-motor function and presence of infarctlesions were used to validate suitability of I/R model for studying mildischemic conditions such as TIA. Additionally, effects of I/R and treatmentwere evaluated on histo/morphological level.Absence of sensory-motor deficits and infarct lesions, as well aspreserved tissue structure and overall neuronal morphology in hippocampusand prefrontal cortex following I/R and treatment were detected indicatingsuitability of used I/R model for investigation of mild ischemic states. Regionspecificpostischemic changes of NMDA receptor/neuronal nitric oxidesynthase/nitric oxide following short-term I/R indicate higher sensitivity ofhippocampus compared to prefrontal cortex. DHEA effect was detectedexclusively following I/R, returning the parameters in prefrontal cortex to thecontrol value, while hippocampal Bax/Bcl-2 ratio and mitochondrial membranepotential changes indicate the initiation of pro-apoptotic events. Therefore,previously reported neuroprotective effect of DHEA should be considered withcaution and further investigated.
PB  - Универзитет у Београду, Биолошки факултет
T2  - Универзитет у Београду
T1  - Efekat kratkotrajne moždane ishemije/reperfuzije i tretmana dehidroepiandrosteronom na komponente signalnog puta NMDA receptora u hipokampusu i prečeonoj kori pacova
ER  - 
@phdthesis{
author = "Zarić, Marina",
year = "2019",
abstract = "Stanje moždane ishemije/reperfuzije (I/R) karakteristično je za cerebrovaskularnaoboljenja kao što su moţdani udar i tranzitorni ishemijski atak(TIA). Promena signalizacije posredovana N-metil-D-aspartat (NMDA)receptorom ima značajnu ulogu u I/R-uzrokovanom oštećenju, dok jedehidroepiandrosteron (DHEA), pozitvni alosterični modulator NMDAreceptora, najčešće okarakterisan kao neuroprotektivan u tretmanu ishemičnihstanja.U ovoj disertaciji ispitivana je proteinska ekspresija komponentikompleksa NMDA receptora i njegove nishodne signalizacije u hipokampusu iprečeonoj kori muţjaka pacova Wistar soja 24 sata nakon podvezivanja obezajedničke karotidne arterije u trajanju od 15 min i/ili efekat tretmana DHEAprimenjenog 4 sata od hirurške procedure. Praćenje senzo-motorne funkcije iprisustvo infarktnih lezija na presecima celog mozga korišćeno je za validacijuI/R modela za proučavanje blaţih ishemičnih stanja poput TIA. Takođe,izvršeno je ispitivanje efekata I/R i tretmana na histo/morfološkom nivou.Odsustvo senzo-motornih deficita i infarktnih lezija kao i očuvanastruktura tkiva i morfologija neurona u hipokampusu i prečeonoj kori nakonI/R ukazuju na potencijalnu primenu modela u ispitivanju umerenihishemičnih stanja. Region-specifične promene signalnog puta NMDAreceptor/neuralna azot oksid sintaza/azot oksid nakon kratkotrajne I/R govoreu prilog većoj osetljivosti hipokampusa u odnosu na prečeonu koru. EfekatDHEA uočen je isključivo nakon I/R, vraćajući u prečeonoj kori parametare nakontrolnu vrednost, dok u hipokampusu promene Bax/Bcl -2 odnosa ipotencijala mitohondrijske membrane ukazuju na pokretanje pro-apoptotskihdešavanja. Stoga, prethodno okarakterisani neuroprotektivni efekat DHEAtreba dodatno istraţiti., Cerebral ischemia/reperfusion (I/R) is characteristic of cerebro-vasculardiseases such as stroke and transient ischemic attack (TIA). Alterations of Nmethyl-D-aspartate (NMDA) receptor-mediated signalling pathway are wellrecognized features of I/R-governed damage, while dehydroepiandrosterone(DHEA), its positive allosteric modulator, has been previously described asneuroprotective and potentially promising for therapy of ischemic conditions.In this doctoral dissertation changes of components of the NMDAreceptor complex and downstream signalling in hippocampus and prefrontalcortex were examined in male Wistar rats 24 h following 15 min bilateralcommon carotid artery occlusion. In addition, effects of 4 h post-surgical DHEAtreatment were investigated. Sensory-motor function and presence of infarctlesions were used to validate suitability of I/R model for studying mildischemic conditions such as TIA. Additionally, effects of I/R and treatmentwere evaluated on histo/morphological level.Absence of sensory-motor deficits and infarct lesions, as well aspreserved tissue structure and overall neuronal morphology in hippocampusand prefrontal cortex following I/R and treatment were detected indicatingsuitability of used I/R model for investigation of mild ischemic states. Regionspecificpostischemic changes of NMDA receptor/neuronal nitric oxidesynthase/nitric oxide following short-term I/R indicate higher sensitivity ofhippocampus compared to prefrontal cortex. DHEA effect was detectedexclusively following I/R, returning the parameters in prefrontal cortex to thecontrol value, while hippocampal Bax/Bcl-2 ratio and mitochondrial membranepotential changes indicate the initiation of pro-apoptotic events. Therefore,previously reported neuroprotective effect of DHEA should be considered withcaution and further investigated.",
publisher = "Универзитет у Београду, Биолошки факултет",
journal = "Универзитет у Београду",
title = "Efekat kratkotrajne moždane ishemije/reperfuzije i tretmana dehidroepiandrosteronom na komponente signalnog puta NMDA receptora u hipokampusu i prečeonoj kori pacova"
}
Zarić, M.. (2019). Efekat kratkotrajne moždane ishemije/reperfuzije i tretmana dehidroepiandrosteronom na komponente signalnog puta NMDA receptora u hipokampusu i prečeonoj kori pacova. in Универзитет у Београду
Универзитет у Београду, Биолошки факултет..
Zarić M. Efekat kratkotrajne moždane ishemije/reperfuzije i tretmana dehidroepiandrosteronom na komponente signalnog puta NMDA receptora u hipokampusu i prečeonoj kori pacova. in Универзитет у Београду. 2019;..
Zarić, Marina, "Efekat kratkotrajne moždane ishemije/reperfuzije i tretmana dehidroepiandrosteronom na komponente signalnog puta NMDA receptora u hipokampusu i prečeonoj kori pacova" in Универзитет у Београду (2019).

Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification

Dragić, Milorad; Zarić, Marina; Mitrović, Nataša Lj.; Nedeljković, Nadežda; Grković, Ivana

(2019)

TY  - JOUR
AU  - Dragić, Milorad
AU  - Zarić, Marina
AU  - Mitrović, Nataša Lj.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2019
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/8489
AB  - Enzyme histochemistry is a valuable histological method which provides a connection between morphology, activity, and spatial localization of investigated enzymes. Even though the method relies purely on arbitrary evaluations performed by the human eye, it is still wildly accepted and used in histo(patho)logy. Texture analysis emerged as an excellent tool for image quantification of subtle differences reflected in both spatial discrepancies and gray level values of pixels. The current study of texture analysis utilizes the gray-level co-occurrence matrix as a method for quantification of differences between ecto-5′-nucleotidase activities in healthy hippocampal tissue and tissue with marked neurodegeneration. We used the angular second moment, contrast (CON), correlation, inverse difference moment (INV), and entropy for texture analysis and receiver operating characteristic analysis with immunoblot and qualitative assessment of enzyme histochemistry as a validation. Our results strongly argue that co-occurrence matrix analysis could be used for the determination of fine differences in the enzyme activities with the possibility to ascribe those differences to regions or specific cell types. In addition, it emerged that INV and CON are especially useful parameters for this type of enzyme histochemistry analysis. We concluded that texture analysis is a reliable method for quantification of this descriptive technique, thus removing biases and adding it a quantitative dimension.
T2  - Microscopy and Microanalysis
T1  - Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification
VL  - 25
IS  - 3
SP  - 690
EP  - 698
DO  - 10.1017/S1431927618016306
ER  - 
@article{
author = "Dragić, Milorad and Zarić, Marina and Mitrović, Nataša Lj. and Nedeljković, Nadežda and Grković, Ivana",
year = "2019",
abstract = "Enzyme histochemistry is a valuable histological method which provides a connection between morphology, activity, and spatial localization of investigated enzymes. Even though the method relies purely on arbitrary evaluations performed by the human eye, it is still wildly accepted and used in histo(patho)logy. Texture analysis emerged as an excellent tool for image quantification of subtle differences reflected in both spatial discrepancies and gray level values of pixels. The current study of texture analysis utilizes the gray-level co-occurrence matrix as a method for quantification of differences between ecto-5′-nucleotidase activities in healthy hippocampal tissue and tissue with marked neurodegeneration. We used the angular second moment, contrast (CON), correlation, inverse difference moment (INV), and entropy for texture analysis and receiver operating characteristic analysis with immunoblot and qualitative assessment of enzyme histochemistry as a validation. Our results strongly argue that co-occurrence matrix analysis could be used for the determination of fine differences in the enzyme activities with the possibility to ascribe those differences to regions or specific cell types. In addition, it emerged that INV and CON are especially useful parameters for this type of enzyme histochemistry analysis. We concluded that texture analysis is a reliable method for quantification of this descriptive technique, thus removing biases and adding it a quantitative dimension.",
journal = "Microscopy and Microanalysis",
title = "Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification",
volume = "25",
number = "3",
pages = "690-698",
doi = "10.1017/S1431927618016306"
}
Dragić, M., Zarić, M., Mitrović, N. Lj., Nedeljković, N.,& Grković, I.. (2019). Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification. in Microscopy and Microanalysis, 25(3), 690-698.
https://doi.org/10.1017/S1431927618016306
Dragić M, Zarić M, Mitrović NL, Nedeljković N, Grković I. Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification. in Microscopy and Microanalysis. 2019;25(3):690-698.
doi:10.1017/S1431927618016306 .
Dragić, Milorad, Zarić, Marina, Mitrović, Nataša Lj., Nedeljković, Nadežda, Grković, Ivana, "Application of Gray Level Co-Occurrence Matrix Analysis as a New Method for Enzyme Histochemistry Quantification" in Microscopy and Microanalysis, 25, no. 3 (2019):690-698,
https://doi.org/10.1017/S1431927618016306 . .
3
6
3
4

Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication

Dragić, Milorad; Zarić, Marina; Mitrović, Nataša Lj.; Nedeljković, Nadežda; Grković, Ivana

(2019)

TY  - JOUR
AU  - Dragić, Milorad
AU  - Zarić, Marina
AU  - Mitrović, Nataša Lj.
AU  - Nedeljković, Nadežda
AU  - Grković, Ivana
PY  - 2019
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/8647
AB  - Astrocytes comprise a heterogenic group of glial cells, which perform homeostatic functions in the central nervous system. These cells react to all kind of insults by changing the morphology and function that result in a transition from the quiescent to a reactive phenotype. Trimethyltin (TMT) intoxication, which reproduces pathological events in the hippocampus similar to those associated with seizures and cognitive decline, has been proven as a useful model for studying responses of the glial cells to neurodegeneration. In the present study, we have explored morphological varieties of astrocytes in the hippocampal subregions of ovariectomized female rats exposed to TMT. We have demonstrated an early loss of neurons in CA1 and DG subfields. Distinct morphotypes of protoplasmic astrocytes observed in CA1/CA3 and the hilus of control animals developed different responses to TMT intoxication, as assessed by GFAP-immunohistochemistry. In CA1 subregion, GFAP+ astrocytes preserved their domain organization and responded with typical hypertrophy, while the hilar GFAP+ astrocytes developed atrophy-like phenotype and increased expression of vimentin and nestin 7 days after the exposure. Both reactive and atrophied-like astrocytes expressed Kir4.1 in CA1/CA3 and the hilus of DG, respectively, indicating that these cells did not change their potential for normal activity at this time point of pathology. Together, the results demonstrate the persistence of two protoplasmic morphotypes of astrocytes, with distinct appearance, function, and fate after TMT-induced neurodegeneration, suggesting their pleiotropic roles in the hippocampal response to neurodegeneration. © 2019 IBRO
T2  - Neuroscience
T1  - Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication
VL  - 423
SP  - 38
EP  - 54
DO  - 10.1016/j.neuroscience.2019.10.022
ER  - 
@article{
author = "Dragić, Milorad and Zarić, Marina and Mitrović, Nataša Lj. and Nedeljković, Nadežda and Grković, Ivana",
year = "2019",
abstract = "Astrocytes comprise a heterogenic group of glial cells, which perform homeostatic functions in the central nervous system. These cells react to all kind of insults by changing the morphology and function that result in a transition from the quiescent to a reactive phenotype. Trimethyltin (TMT) intoxication, which reproduces pathological events in the hippocampus similar to those associated with seizures and cognitive decline, has been proven as a useful model for studying responses of the glial cells to neurodegeneration. In the present study, we have explored morphological varieties of astrocytes in the hippocampal subregions of ovariectomized female rats exposed to TMT. We have demonstrated an early loss of neurons in CA1 and DG subfields. Distinct morphotypes of protoplasmic astrocytes observed in CA1/CA3 and the hilus of control animals developed different responses to TMT intoxication, as assessed by GFAP-immunohistochemistry. In CA1 subregion, GFAP+ astrocytes preserved their domain organization and responded with typical hypertrophy, while the hilar GFAP+ astrocytes developed atrophy-like phenotype and increased expression of vimentin and nestin 7 days after the exposure. Both reactive and atrophied-like astrocytes expressed Kir4.1 in CA1/CA3 and the hilus of DG, respectively, indicating that these cells did not change their potential for normal activity at this time point of pathology. Together, the results demonstrate the persistence of two protoplasmic morphotypes of astrocytes, with distinct appearance, function, and fate after TMT-induced neurodegeneration, suggesting their pleiotropic roles in the hippocampal response to neurodegeneration. © 2019 IBRO",
journal = "Neuroscience",
title = "Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication",
volume = "423",
pages = "38-54",
doi = "10.1016/j.neuroscience.2019.10.022"
}
Dragić, M., Zarić, M., Mitrović, N. Lj., Nedeljković, N.,& Grković, I.. (2019). Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication. in Neuroscience, 423, 38-54.
https://doi.org/10.1016/j.neuroscience.2019.10.022
Dragić M, Zarić M, Mitrović NL, Nedeljković N, Grković I. Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication. in Neuroscience. 2019;423:38-54.
doi:10.1016/j.neuroscience.2019.10.022 .
Dragić, Milorad, Zarić, Marina, Mitrović, Nataša Lj., Nedeljković, Nadežda, Grković, Ivana, "Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication" in Neuroscience, 423 (2019):38-54,
https://doi.org/10.1016/j.neuroscience.2019.10.022 . .
2
6
3
3

Melatonin modulate the expression of α1- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress

Stefanović, Bojana; Spasojević, Nataša; Jovanović, Predrag; Ferizović, Harisa; Dronjak, Slađana

(2018)

TY  - JOUR
AU  - Stefanović, Bojana
AU  - Spasojević, Nataša
AU  - Jovanović, Predrag
AU  - Ferizović, Harisa
AU  - Dronjak, Slađana
PY  - 2018
UR  - https://www.scopus.com/inward/record.uri?eid=2-s2.0-85050161804&doi=10.4149%2FBLL_2018_078&partnerID=40&md5=d2052d74db7eec104ae62eb2ce214831
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/7795
AB  - OBJECTIVE: This study investigated the effects of chronic melatonin treatment on gene expression of α1-, α2-, β1- and β2-adrenoceptors in the hippocampus of rats subjected to chronic unpredictable mild stress (CUMS). BACKGROUND: Preclinical studies have also shown that melatonin prevented short- and long-term memory impairments and exhibited antidepressant-like actions. METHODS: For this study, we used 24 animals, which were divided into four groups, and the experiment lasted 4 weeks. We quantifi ed the changes in mRNA and protein levels of α1-, α2-, β1- and β2-adrenoceptors in the hippocampus after melatonin treatment. RESULTS: Our results demonstrated a decreased gene expression of α1-, α2- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress, while there was no change in gene expression of β1-adrenoceptors. Melatonin treatment in the CUMS rats prevented the stress-induced decrease in mRNA and protein levels of α1-and β2-adrenoceptors, whereas did not affect either on mRNA or protein level of β1-and α2-adrenoceptors. CONCLUSION: Our data suggest that melatonin, by increasing reduced levels of α1- and β2-adrenoceptors mRNA and protein in the hippocampus of chronic stressed rats, may be benefi cial in conditions such as chronic stress and provides an experimental opportunity to probe into further molecular mechanisms underlying the regulation of these receptor subtype.
T2  - Bratislava Medical Journal
T1  - Melatonin modulate the expression of α1- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress
VL  - 119
IS  - 7
SP  - 429
EP  - 433
DO  - 10.4149/BLL_2018_078
ER  - 
@article{
author = "Stefanović, Bojana and Spasojević, Nataša and Jovanović, Predrag and Ferizović, Harisa and Dronjak, Slađana",
year = "2018",
abstract = "OBJECTIVE: This study investigated the effects of chronic melatonin treatment on gene expression of α1-, α2-, β1- and β2-adrenoceptors in the hippocampus of rats subjected to chronic unpredictable mild stress (CUMS). BACKGROUND: Preclinical studies have also shown that melatonin prevented short- and long-term memory impairments and exhibited antidepressant-like actions. METHODS: For this study, we used 24 animals, which were divided into four groups, and the experiment lasted 4 weeks. We quantifi ed the changes in mRNA and protein levels of α1-, α2-, β1- and β2-adrenoceptors in the hippocampus after melatonin treatment. RESULTS: Our results demonstrated a decreased gene expression of α1-, α2- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress, while there was no change in gene expression of β1-adrenoceptors. Melatonin treatment in the CUMS rats prevented the stress-induced decrease in mRNA and protein levels of α1-and β2-adrenoceptors, whereas did not affect either on mRNA or protein level of β1-and α2-adrenoceptors. CONCLUSION: Our data suggest that melatonin, by increasing reduced levels of α1- and β2-adrenoceptors mRNA and protein in the hippocampus of chronic stressed rats, may be benefi cial in conditions such as chronic stress and provides an experimental opportunity to probe into further molecular mechanisms underlying the regulation of these receptor subtype.",
journal = "Bratislava Medical Journal",
title = "Melatonin modulate the expression of α1- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress",
volume = "119",
number = "7",
pages = "429-433",
doi = "10.4149/BLL_2018_078"
}
Stefanović, B., Spasojević, N., Jovanović, P., Ferizović, H.,& Dronjak, S.. (2018). Melatonin modulate the expression of α1- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress. in Bratislava Medical Journal, 119(7), 429-433.
https://doi.org/10.4149/BLL_2018_078
Stefanović B, Spasojević N, Jovanović P, Ferizović H, Dronjak S. Melatonin modulate the expression of α1- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress. in Bratislava Medical Journal. 2018;119(7):429-433.
doi:10.4149/BLL_2018_078 .
Stefanović, Bojana, Spasojević, Nataša, Jovanović, Predrag, Ferizović, Harisa, Dronjak, Slađana, "Melatonin modulate the expression of α1- and β2-adrenoceptors in the hippocampus of rats subjected to unpredictable chronic mild stress" in Bratislava Medical Journal, 119, no. 7 (2018):429-433,
https://doi.org/10.4149/BLL_2018_078 . .
2
2
2

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  - http://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
16
14
16

Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats

Zarić, Marina; Drakulić, Dunja R.; Guševac Stojanović, Ivana; Mitrović, Nataša Lj.; Grković, Ivana; Martinović, Jelena

(2018)

TY  - JOUR
AU  - Zarić, Marina
AU  - Drakulić, Dunja R.
AU  - Guševac Stojanović, Ivana
AU  - Mitrović, Nataša Lj.
AU  - Grković, Ivana
AU  - Martinović, Jelena
PY  - 2018
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0006899318301586
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/7626
AB  - Excessive glutamate efflux and N-methyl-D-aspartate receptor (NMDAR) over -activation represent wellknown hallmarks of cerebral ischemia/reperfusion (I/R) injury, still, expression of proteins involved in this aspect of I/R pathophysiology show inconsistent data. Neurosteroid dehydroepiandrosterone (DHEA) has been proposed as potent NMDAR modulator, but its influence on I/R-induced changes up to date remains questionable. Therefore, I/R-governed alteration of vesicular glutamate transporter 1 (vGluT1), synaptic NMDAR subunit composition, postsynaptic density protein 95 (PSD-95) and neuronal morphology alone or following DHEA treatment were examined. For that purpose, adult male Wistar rats were treated with a single dose of vehicle or DHEA (20 mg/kg i.p.) 4 h following sham operation or 15 min bilateral common carotid artery occlusion. Western blot was used for analyses of synaptic protein expressions in hippocampus and prefrontal cortex, while neuronal morphology was assessed using Nissl staining. Regional -specific postischemic changes were detected on protein level i.e. signs of neuronal damage in CA1 area was accompanied with hippocampal vGluT1, NR1, NR2B enhancement and PSD-95 decrement, while histological changes observed in layer III were associated with decreased NR1 subunit in prefrontal cortex. Under physiological conditions DHEA had no effect on protein and histological appearance, while in ischemic milieu it restored hippocampal PSD-95 and NR1 in prefrontal cortex to the control level. Along with intact neurons, ones characterized by morphology observed in I/R group were also present. Future studies involving NMDAR-related intracellular signaling and immunohistochemical analysis will reveal precise effects of I/R and DHEA treatment in selected brain regions. (C) 2018 Elsevier B.V. All rights reserved.
T2  - Brain Research
T1  - Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats
VL  - 1688
SP  - 73
EP  - 80
DO  - 10.1016/j.brainres.2018.03.023
ER  - 
@article{
author = "Zarić, Marina and Drakulić, Dunja R. and Guševac Stojanović, Ivana and Mitrović, Nataša Lj. and Grković, Ivana and Martinović, Jelena",
year = "2018",
abstract = "Excessive glutamate efflux and N-methyl-D-aspartate receptor (NMDAR) over -activation represent wellknown hallmarks of cerebral ischemia/reperfusion (I/R) injury, still, expression of proteins involved in this aspect of I/R pathophysiology show inconsistent data. Neurosteroid dehydroepiandrosterone (DHEA) has been proposed as potent NMDAR modulator, but its influence on I/R-induced changes up to date remains questionable. Therefore, I/R-governed alteration of vesicular glutamate transporter 1 (vGluT1), synaptic NMDAR subunit composition, postsynaptic density protein 95 (PSD-95) and neuronal morphology alone or following DHEA treatment were examined. For that purpose, adult male Wistar rats were treated with a single dose of vehicle or DHEA (20 mg/kg i.p.) 4 h following sham operation or 15 min bilateral common carotid artery occlusion. Western blot was used for analyses of synaptic protein expressions in hippocampus and prefrontal cortex, while neuronal morphology was assessed using Nissl staining. Regional -specific postischemic changes were detected on protein level i.e. signs of neuronal damage in CA1 area was accompanied with hippocampal vGluT1, NR1, NR2B enhancement and PSD-95 decrement, while histological changes observed in layer III were associated with decreased NR1 subunit in prefrontal cortex. Under physiological conditions DHEA had no effect on protein and histological appearance, while in ischemic milieu it restored hippocampal PSD-95 and NR1 in prefrontal cortex to the control level. Along with intact neurons, ones characterized by morphology observed in I/R group were also present. Future studies involving NMDAR-related intracellular signaling and immunohistochemical analysis will reveal precise effects of I/R and DHEA treatment in selected brain regions. (C) 2018 Elsevier B.V. All rights reserved.",
journal = "Brain Research",
title = "Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats",
volume = "1688",
pages = "73-80",
doi = "10.1016/j.brainres.2018.03.023"
}
Zarić, M., Drakulić, D. R., Guševac Stojanović, I., Mitrović, N. Lj., Grković, I.,& Martinović, J.. (2018). Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats. in Brain Research, 1688, 73-80.
https://doi.org/10.1016/j.brainres.2018.03.023
Zarić M, Drakulić DR, Guševac Stojanović I, Mitrović NL, Grković I, Martinović J. Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats. in Brain Research. 2018;1688:73-80.
doi:10.1016/j.brainres.2018.03.023 .
Zarić, Marina, Drakulić, Dunja R., Guševac Stojanović, Ivana, Mitrović, Nataša Lj., Grković, Ivana, Martinović, Jelena, "Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats" in Brain Research, 1688 (2018):73-80,
https://doi.org/10.1016/j.brainres.2018.03.023 . .
5
6
6

TIMP-3 mRNA expression levels positively correlates with levels of miR-21 in in situ BC and negatively in PR positive invasive BC

Petrović, Nina; Sami, Ahmad; Martinović, Jelena; Zarić, Marina; Nakashidze, Irina; Lukić, Silvana; Jovanović-Ćupić, Snežana P.

(2017)

TY  - JOUR
AU  - Petrović, Nina
AU  - Sami, Ahmad
AU  - Martinović, Jelena
AU  - Zarić, Marina
AU  - Nakashidze, Irina
AU  - Lukić, Silvana
AU  - Jovanović-Ćupić, Snežana P.
PY  - 2017
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/1805
AB  - Background: Breast carcinomas (BC) belong to a heterogeneous group of malignant diseases. Correct categorization of BC based on molecular biomarkers has a very important role in deciding the proper course of therapy for each patient. It has been already shown that the decrease of TIMP metalloproteinase inhibitor 3 (TIMP-3) together with overexpression of microRNA-21 (miR-21) might be involved in the process of BC invasion. This is the first study that examined relationship among miR-21, TIMP-3 mRNA and TIPM-3 protein levels in BC groups formed according to invasiveness. Methods: In this study, we used 46 breast cancer samples. Estrogen and progesterone receptor (ER, PR) protein levels were evaluated by immunohistochemistry (IHC) method. TIMP-3 mRNA expression was examined by two-step real-time quantitative PCR (qRT-PCR). Western blot analysis was performed for 16 samples. Results: Statistically significant differences in TIMP-3 expression levels between invasive groups were discovered in ER positive (ER+) (p = 0.015), Her-2 negative (p = 0.026) subgroups, and patients without lymph-node metastasis (p = 0.039). Interestingly, significant positive correlation was detected between miR-21 and TIMP-3 mRNA levels (P LT 0.001, p = 0.949) in the group of in situ tumors. TIMP-3 mRNA expression levels highly negatively correlated with levels of miR-21 in PR + invasive BCs (p = 0.007, p = -0.641). TIMP-3 protein levels negatively correlated with miR-21 levels in pure invasive BCs. Conclusion: These data suggest that signaling pathways involved in formation and progression of BCs in groups formed according to invasiveness might be different. Our findings propose that TIMP-3 mRNA expression levels could be significant prognostic parameter, but within specific BC subtypes.
T2  - Pathology Research and Practice
T1  - TIMP-3 mRNA expression levels positively correlates with levels of miR-21 in in situ BC and negatively in PR positive invasive BC
VL  - 213
IS  - 10
SP  - 1264
EP  - 1270
DO  - 10.1016/j.prp.2017.08.012
ER  - 
@article{
author = "Petrović, Nina and Sami, Ahmad and Martinović, Jelena and Zarić, Marina and Nakashidze, Irina and Lukić, Silvana and Jovanović-Ćupić, Snežana P.",
year = "2017",
abstract = "Background: Breast carcinomas (BC) belong to a heterogeneous group of malignant diseases. Correct categorization of BC based on molecular biomarkers has a very important role in deciding the proper course of therapy for each patient. It has been already shown that the decrease of TIMP metalloproteinase inhibitor 3 (TIMP-3) together with overexpression of microRNA-21 (miR-21) might be involved in the process of BC invasion. This is the first study that examined relationship among miR-21, TIMP-3 mRNA and TIPM-3 protein levels in BC groups formed according to invasiveness. Methods: In this study, we used 46 breast cancer samples. Estrogen and progesterone receptor (ER, PR) protein levels were evaluated by immunohistochemistry (IHC) method. TIMP-3 mRNA expression was examined by two-step real-time quantitative PCR (qRT-PCR). Western blot analysis was performed for 16 samples. Results: Statistically significant differences in TIMP-3 expression levels between invasive groups were discovered in ER positive (ER+) (p = 0.015), Her-2 negative (p = 0.026) subgroups, and patients without lymph-node metastasis (p = 0.039). Interestingly, significant positive correlation was detected between miR-21 and TIMP-3 mRNA levels (P LT 0.001, p = 0.949) in the group of in situ tumors. TIMP-3 mRNA expression levels highly negatively correlated with levels of miR-21 in PR + invasive BCs (p = 0.007, p = -0.641). TIMP-3 protein levels negatively correlated with miR-21 levels in pure invasive BCs. Conclusion: These data suggest that signaling pathways involved in formation and progression of BCs in groups formed according to invasiveness might be different. Our findings propose that TIMP-3 mRNA expression levels could be significant prognostic parameter, but within specific BC subtypes.",
journal = "Pathology Research and Practice",
title = "TIMP-3 mRNA expression levels positively correlates with levels of miR-21 in in situ BC and negatively in PR positive invasive BC",
volume = "213",
number = "10",
pages = "1264-1270",
doi = "10.1016/j.prp.2017.08.012"
}
Petrović, N., Sami, A., Martinović, J., Zarić, M., Nakashidze, I., Lukić, S.,& Jovanović-Ćupić, S. P.. (2017). TIMP-3 mRNA expression levels positively correlates with levels of miR-21 in in situ BC and negatively in PR positive invasive BC. in Pathology Research and Practice, 213(10), 1264-1270.
https://doi.org/10.1016/j.prp.2017.08.012
Petrović N, Sami A, Martinović J, Zarić M, Nakashidze I, Lukić S, Jovanović-Ćupić SP. TIMP-3 mRNA expression levels positively correlates with levels of miR-21 in in situ BC and negatively in PR positive invasive BC. in Pathology Research and Practice. 2017;213(10):1264-1270.
doi:10.1016/j.prp.2017.08.012 .
Petrović, Nina, Sami, Ahmad, Martinović, Jelena, Zarić, Marina, Nakashidze, Irina, Lukić, Silvana, Jovanović-Ćupić, Snežana P., "TIMP-3 mRNA expression levels positively correlates with levels of miR-21 in in situ BC and negatively in PR positive invasive BC" in Pathology Research and Practice, 213, no. 10 (2017):1264-1270,
https://doi.org/10.1016/j.prp.2017.08.012 . .
4
4
4

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  - http://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 . .
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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  - http://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 . .
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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  - http://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 . .
8
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7

17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes

Mitrović, Nataša Lj.; Zarić, Marina; Drakulić, Dunja R.; Martinović, Jelena; Sevigny, Jean; Stanojlović, Miloš R.; Nedeljkovic, Nadezda; Grković, Ivana

(2017)

TY  - JOUR
AU  - Mitrović, Nataša Lj.
AU  - Zarić, Marina
AU  - Drakulić, Dunja R.
AU  - Martinović, Jelena
AU  - Sevigny, Jean
AU  - Stanojlović, Miloš R.
AU  - Nedeljkovic, Nadezda
AU  - Grković, Ivana
PY  - 2017
UR  - http://vinar.vin.bg.ac.rs/handle/123456789/1459
AB  - 17 beta-Estradiol (E2) rapidly, by binding to membrane estrogen receptors, activates cell signaling cascades which induce formation of new dendritic spines in the hippocampus of males as in females, but the interaction with other metabolic processes, such as extracellular adenine nucleotides metabolism, are currently unknown. Extracellular adenine nucleotides play significant roles, controlling excitatory glutamatergic synapses and development of neural circuits and synaptic plasticity. Their precise regulation in the synaptic cleft is tightly controlled by ecto-nucleoside triphosphate diphosphohydrolase (NTPDase)/ecto-5-nucleotidase (eN) enzyme chain. Therefore, we sought to clarify whether a single systemic injection of E2 in male rats is accompanied by changes in the expression of the pre- and postsynaptic proteins and downstream kinases linked to E2-induced synaptic rearrangement as well as alterations in NTPDase/eN pathway in the hippocampal synaptosomes. Obtained data showed activation of mammalian target of rapamycin and upregulation of key synaptic proteins necessary for spine formation, 24 h after systemic E2 administration. In E2-mediated conditions, we found downregulation of NTPDase1 and NTPDase2 and attenuation of adenine nucleotide hydrolysis by NTPDase/eN enzyme chain, without changes in NTPDase3 properties and augmentation of synaptic tissue-nonspecific alkaline phosphatase (TNAP) activity. Despite reduced NTPDase activities, increased TNAP activity probably prevents toxic accumulation of ATP in the extracellular milieu and also hydrolyzes accumulated ADP due to unchanged NTPDase3 activity. Thus, our initial evaluation supports idea of specific roles of different ectonucleotidases and their coordinated actions in E2-mediated spine remodeling and maintenance.
T2  - Journal of Molecular Neuroscience
T1  - 17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes
VL  - 61
IS  - 3
SP  - 412
EP  - 422
DO  - 10.1007/s12031-016-0877-6
ER  - 
@article{
author = "Mitrović, Nataša Lj. and Zarić, Marina and Drakulić, Dunja R. and Martinović, Jelena and Sevigny, Jean and Stanojlović, Miloš R. and Nedeljkovic, Nadezda and Grković, Ivana",
year = "2017",
abstract = "17 beta-Estradiol (E2) rapidly, by binding to membrane estrogen receptors, activates cell signaling cascades which induce formation of new dendritic spines in the hippocampus of males as in females, but the interaction with other metabolic processes, such as extracellular adenine nucleotides metabolism, are currently unknown. Extracellular adenine nucleotides play significant roles, controlling excitatory glutamatergic synapses and development of neural circuits and synaptic plasticity. Their precise regulation in the synaptic cleft is tightly controlled by ecto-nucleoside triphosphate diphosphohydrolase (NTPDase)/ecto-5-nucleotidase (eN) enzyme chain. Therefore, we sought to clarify whether a single systemic injection of E2 in male rats is accompanied by changes in the expression of the pre- and postsynaptic proteins and downstream kinases linked to E2-induced synaptic rearrangement as well as alterations in NTPDase/eN pathway in the hippocampal synaptosomes. Obtained data showed activation of mammalian target of rapamycin and upregulation of key synaptic proteins necessary for spine formation, 24 h after systemic E2 administration. In E2-mediated conditions, we found downregulation of NTPDase1 and NTPDase2 and attenuation of adenine nucleotide hydrolysis by NTPDase/eN enzyme chain, without changes in NTPDase3 properties and augmentation of synaptic tissue-nonspecific alkaline phosphatase (TNAP) activity. Despite reduced NTPDase activities, increased TNAP activity probably prevents toxic accumulation of ATP in the extracellular milieu and also hydrolyzes accumulated ADP due to unchanged NTPDase3 activity. Thus, our initial evaluation supports idea of specific roles of different ectonucleotidases and their coordinated actions in E2-mediated spine remodeling and maintenance.",
journal = "Journal of Molecular Neuroscience",
title = "17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes",
volume = "61",
number = "3",
pages = "412-422",
doi = "10.1007/s12031-016-0877-6"
}
Mitrović, N. Lj., Zarić, M., Drakulić, D. R., Martinović, J., Sevigny, J., Stanojlović, M. R., Nedeljkovic, N.,& Grković, I.. (2017). 17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes. in Journal of Molecular Neuroscience, 61(3), 412-422.
https://doi.org/10.1007/s12031-016-0877-6
Mitrović NL, Zarić M, Drakulić DR, Martinović J, Sevigny J, Stanojlović MR, Nedeljkovic N, Grković I. 17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes. in Journal of Molecular Neuroscience. 2017;61(3):412-422.
doi:10.1007/s12031-016-0877-6 .
Mitrović, Nataša Lj., Zarić, Marina, Drakulić, Dunja R., Martinović, Jelena, Sevigny, Jean, Stanojlović, Miloš R., Nedeljkovic, Nadezda, Grković, Ivana, "17 beta-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes" in Journal of Molecular Neuroscience, 61, no. 3 (2017):412-422,
https://doi.org/10.1007/s12031-016-0877-6 . .
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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  - http://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 . .
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