TY  - JOUR
AU  - Đorđević, Jelena
AU  - Đorđević, Ana
AU  - Adžić, Miroslav
AU  - Mitić, Milos
AU  - Lukić, Iva
AU  - Radojcić, Marija B
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/682
AB  - Knowledge of the antioxidant defense in the stress-responding structures of the CNS is of crucial importance, since oxidative damage is a phenomenon accompanying many stress-related disorders. Regulation of antioxidative and anti-inflammatory defense through Nrf2 (nuclear factor 2 eritroid related factor 2) pathway has emerged as a promising approach for neuroprotection. In this study, we used chronic social isolation of male Wistar rats to induce depressive-like behavior. We hypothesized that Nrf2 Keap1 pathway is compromised in the limbic brain after prolonged stress. Since subcellular trafficking of Nrf2 and its inhibitor Keap1 (Kelch ECH associating protein 1) is essential for the activation of Nrf2, we determined their protein level in cytosolic and nuclear comp& linents of hippocampus and prefrontal cortex (PEG). We also determined mRNA levels of Nr12-regulated genes involved in the production and utilization of glutathione, glutamate cysteine ligase (Gclm), glutathione S-transferase (Gsta3) and glutathione reductase (Gsr). Our results showed that chronic isolation induced anxiety and depressive-like behavior, decreased Nrf2 and in parallel increased Keap1 and nuclear factor kappa B (NF kappa B) in the hippocampus, which were not accompanied by expression profiles of Nrf2-regulated genes. Chronically stressed rats challenged with acute stress failed to induce any response of examined genes in either of brain structures, even though Nrf2/Keap1 was altered, while in naive animals Nrf2 activity corresponded witli an expression of Nrf2-regulated genes. Our results reveal maladaptive character of chronic stress at Nrf2/Keap1 level followed by pro-inflammatory conditions, and suggest a possible role of these alterations in pathogenesis of depressive/anxiety disorders. (C) 2015 Elsevier B.V. All rights reserved.
T2  - Brain Research
T1  - Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress
IS  - null
VL  - 1602
SP  - 19
EP  - 31
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_682
ER  - 

@article{
author = "Đorđević, Jelena and Đorđević, Ana and Adžić, Miroslav and Mitić, Milos and Lukić, Iva and Radojcić, Marija B",
year = "2015",
abstract = "Knowledge of the antioxidant defense in the stress-responding structures of the CNS is of crucial importance, since oxidative damage is a phenomenon accompanying many stress-related disorders. Regulation of antioxidative and anti-inflammatory defense through Nrf2 (nuclear factor 2 eritroid related factor 2) pathway has emerged as a promising approach for neuroprotection. In this study, we used chronic social isolation of male Wistar rats to induce depressive-like behavior. We hypothesized that Nrf2 Keap1 pathway is compromised in the limbic brain after prolonged stress. Since subcellular trafficking of Nrf2 and its inhibitor Keap1 (Kelch ECH associating protein 1) is essential for the activation of Nrf2, we determined their protein level in cytosolic and nuclear comp& linents of hippocampus and prefrontal cortex (PEG). We also determined mRNA levels of Nr12-regulated genes involved in the production and utilization of glutathione, glutamate cysteine ligase (Gclm), glutathione S-transferase (Gsta3) and glutathione reductase (Gsr). Our results showed that chronic isolation induced anxiety and depressive-like behavior, decreased Nrf2 and in parallel increased Keap1 and nuclear factor kappa B (NF kappa B) in the hippocampus, which were not accompanied by expression profiles of Nrf2-regulated genes. Chronically stressed rats challenged with acute stress failed to induce any response of examined genes in either of brain structures, even though Nrf2/Keap1 was altered, while in naive animals Nrf2 activity corresponded witli an expression of Nrf2-regulated genes. Our results reveal maladaptive character of chronic stress at Nrf2/Keap1 level followed by pro-inflammatory conditions, and suggest a possible role of these alterations in pathogenesis of depressive/anxiety disorders. (C) 2015 Elsevier B.V. All rights reserved.",
journal = "Brain Research",
title = "Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress",
number = "null",
volume = "1602",
pages = "19-31",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_682"
}

Đorđević, J., Đorđević, A., Adžić, M., Mitić, M., Lukić, I.,& Radojcić, M. B.. (2015). Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress. in Brain Research, 1602(null), 19-31.
https://hdl.handle.net/21.15107/rcub_ibiss_682

Đorđević J, Đorđević A, Adžić M, Mitić M, Lukić I, Radojcić MB. Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress. in Brain Research. 2015;1602(null):19-31.
https://hdl.handle.net/21.15107/rcub_ibiss_682 .

Đorđević, Jelena, Đorđević, Ana, Adžić, Miroslav, Mitić, Milos, Lukić, Iva, Radojcić, Marija B, "Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress" in Brain Research, 1602, no. null (2015):19-31,
https://hdl.handle.net/21.15107/rcub_ibiss_682 .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Lukić, Iva
AU  - Mitić, Milos Z
AU  - Đorđević, Jelena D
AU  - Elaković, Ivana
AU  - Đorđević, Ana
AU  - Krstić-Demonacos, Marija
AU  - Matić, Gordana
AU  - Radojcić, Marija B
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/940
AB  - Antidepressants affect glucocorticoid receptor (GR) functioning partly through modulation of its phosphorylation but their effects on mitochondrial GR have remained undefined. We investigated the ability of chronic fiuoxetine treatment to affect chronic stress-induced changes of mitochondrial GR and its phosphoisoforms (pGRs) in the prefrontal cortex and hippocampus of female and male rats. Since mitochondrial GR regulates oxidative phosphorylation, expression of mitochondrial-encoded subunits of cytochrome (cyt) c oxidase and its activity were also investigated. Chronic stress caused accumulation of the GR in mitochondria of female prefrontal cortex, while the changes in the hippocampus were sex-specific at the levels of pGRs. Expression of mitochondrial COXs genes corresponded to chronic stress-modulated mitochondrial GR in both tissues of both genders and to cyt c oxidase activity in females. Moreover, the metabolic parameters in stressed animals were affected by fiuoxetine therapy only in the hippocampus. Namely, fluoxetine effects on mitochondrial COXs and cyt c oxidase activity in the hippocampus seem to be conveyed through pGR232 in females, while in males this likely occurs through other mechanisms. In summary, sex-specific regulation of cyt c oxidase by the stress and antidepressant treatment and its differential convergence with mitochondrial GR signaling in the prefrontal cortex and hippocampus could contribute to clarification of sex-dependent vulnerability to stress-related disorders and sex-specific clinical impact of antidepressants. (C) 2013 Elsevier Ltd. All rights reserved.
T2  - Psychoneuroendocrinology
T1  - Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism
IS  - 12
VL  - 38
SP  - 1459
EP  - 2924
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_940
ER  - 

@article{
author = "Adžić, Miroslav and Lukić, Iva and Mitić, Milos Z and Đorđević, Jelena D and Elaković, Ivana and Đorđević, Ana and Krstić-Demonacos, Marija and Matić, Gordana and Radojcić, Marija B",
year = "2013",
abstract = "Antidepressants affect glucocorticoid receptor (GR) functioning partly through modulation of its phosphorylation but their effects on mitochondrial GR have remained undefined. We investigated the ability of chronic fiuoxetine treatment to affect chronic stress-induced changes of mitochondrial GR and its phosphoisoforms (pGRs) in the prefrontal cortex and hippocampus of female and male rats. Since mitochondrial GR regulates oxidative phosphorylation, expression of mitochondrial-encoded subunits of cytochrome (cyt) c oxidase and its activity were also investigated. Chronic stress caused accumulation of the GR in mitochondria of female prefrontal cortex, while the changes in the hippocampus were sex-specific at the levels of pGRs. Expression of mitochondrial COXs genes corresponded to chronic stress-modulated mitochondrial GR in both tissues of both genders and to cyt c oxidase activity in females. Moreover, the metabolic parameters in stressed animals were affected by fiuoxetine therapy only in the hippocampus. Namely, fluoxetine effects on mitochondrial COXs and cyt c oxidase activity in the hippocampus seem to be conveyed through pGR232 in females, while in males this likely occurs through other mechanisms. In summary, sex-specific regulation of cyt c oxidase by the stress and antidepressant treatment and its differential convergence with mitochondrial GR signaling in the prefrontal cortex and hippocampus could contribute to clarification of sex-dependent vulnerability to stress-related disorders and sex-specific clinical impact of antidepressants. (C) 2013 Elsevier Ltd. All rights reserved.",
journal = "Psychoneuroendocrinology",
title = "Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism",
number = "12",
volume = "38",
pages = "1459-2924",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_940"
}

Adžić, M., Lukić, I., Mitić, M. Z., Đorđević, J. D., Elaković, I., Đorđević, A., Krstić-Demonacos, M., Matić, G.,& Radojcić, M. B.. (2013). Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism. in Psychoneuroendocrinology, 38(12), 1459-2924.
https://hdl.handle.net/21.15107/rcub_ibiss_940

Adžić M, Lukić I, Mitić MZ, Đorđević JD, Elaković I, Đorđević A, Krstić-Demonacos M, Matić G, Radojcić MB. Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism. in Psychoneuroendocrinology. 2013;38(12):1459-2924.
https://hdl.handle.net/21.15107/rcub_ibiss_940 .

Adžić, Miroslav, Lukić, Iva, Mitić, Milos Z, Đorđević, Jelena D, Elaković, Ivana, Đorđević, Ana, Krstić-Demonacos, Marija, Matić, Gordana, Radojcić, Marija B, "Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism" in Psychoneuroendocrinology, 38, no. 12 (2013):1459-2924,
https://hdl.handle.net/21.15107/rcub_ibiss_940 .