TY  - CONF
AU  - Živanović, Ana
AU  - Mitić, Miloš
AU  - Glavonić, Emilija
AU  - Lukić, Iva
AU  - Adžić, Miroslav
AU  - Ivković, Sanja
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11052
AB  - Major depressive disorder (MDD) affects over 300 million people worldwide. The administration of the sub-anaesthetic dose of ketamine, an NMDAr antagonist, was recently approved as highly effective antidepressant whose therapeutic effects are associated with an increase in BDNF levels in the brain. However, lowering the effective dose of ketamine because of its adverse effects is an important goal. We assessed the changes in BDNF levels after the single administration of two subanesthetic doses of ketamine (6mg/kg, Ket6 and 10mg/kg, Ket10) in the chronic unpredictable stress (CUS) mouse model of depression-like behavior in different brain structures. Male C57BL/6J mice exposed to CUS were treated at the postnatal day 70 with either vehicle, Ket6, or Ket10. Following tail suspension test (TST), to assess depressive phenotype at 2- and 7-days post-treatment, animals were sacrificed and the prefrontal cortex (PFC), hippocampus, and striatum were isolated and processed for Western blot analyses. Statistical significance was determined by 1-way ANOVA. Only Ket6 achieved an antidepressant effect that was extinguished at 7 days. Both doses caused a significant increase in BDNF levels in the striatum while neither dose was able to induce BDNF levels in the hippocampus. The increase in BDNF levels in the PFC was observed only 7 days after the treatment and only with Ket10. The increase in BDNF levels was the greatest in the striatum when it correlated with the antidepressive effects of ketamine. Although this increase was sustained for 7 days it did not correlate with the antidepressive behavior which was already extinguished.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - The effect of different subanesthetic doses of ketamine on BDNF levels in different brain structures in the mouse model of depression
SP  - 83
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11052
ER  - 

@conference{
author = "Živanović, Ana and Mitić, Miloš and Glavonić, Emilija and Lukić, Iva and Adžić, Miroslav and Ivković, Sanja",
year = "2023",
abstract = "Major depressive disorder (MDD) affects over 300 million people worldwide. The administration of the sub-anaesthetic dose of ketamine, an NMDAr antagonist, was recently approved as highly effective antidepressant whose therapeutic effects are associated with an increase in BDNF levels in the brain. However, lowering the effective dose of ketamine because of its adverse effects is an important goal. We assessed the changes in BDNF levels after the single administration of two subanesthetic doses of ketamine (6mg/kg, Ket6 and 10mg/kg, Ket10) in the chronic unpredictable stress (CUS) mouse model of depression-like behavior in different brain structures. Male C57BL/6J mice exposed to CUS were treated at the postnatal day 70 with either vehicle, Ket6, or Ket10. Following tail suspension test (TST), to assess depressive phenotype at 2- and 7-days post-treatment, animals were sacrificed and the prefrontal cortex (PFC), hippocampus, and striatum were isolated and processed for Western blot analyses. Statistical significance was determined by 1-way ANOVA. Only Ket6 achieved an antidepressant effect that was extinguished at 7 days. Both doses caused a significant increase in BDNF levels in the striatum while neither dose was able to induce BDNF levels in the hippocampus. The increase in BDNF levels in the PFC was observed only 7 days after the treatment and only with Ket10. The increase in BDNF levels was the greatest in the striatum when it correlated with the antidepressive effects of ketamine. Although this increase was sustained for 7 days it did not correlate with the antidepressive behavior which was already extinguished.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "The effect of different subanesthetic doses of ketamine on BDNF levels in different brain structures in the mouse model of depression",
pages = "83",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11052"
}

Živanović, A., Mitić, M., Glavonić, E., Lukić, I., Adžić, M.,& Ivković, S.. (2023). The effect of different subanesthetic doses of ketamine on BDNF levels in different brain structures in the mouse model of depression. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neuroscience Society., 83.
https://hdl.handle.net/21.15107/rcub_vinar_11052

Živanović A, Mitić M, Glavonić E, Lukić I, Adžić M, Ivković S. The effect of different subanesthetic doses of ketamine on BDNF levels in different brain structures in the mouse model of depression. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:83.
https://hdl.handle.net/21.15107/rcub_vinar_11052 .

Živanović, Ana, Mitić, Miloš, Glavonić, Emilija, Lukić, Iva, Adžić, Miroslav, Ivković, Sanja, "The effect of different subanesthetic doses of ketamine on BDNF levels in different brain structures in the mouse model of depression" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):83,
https://hdl.handle.net/21.15107/rcub_vinar_11052 .

TY  - CONF
AU  - Glavonić, Emilija
AU  - Aleksić, Minja
AU  - Francija, Ester
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Ivković, Sanja
AU  - Adžić, Miroslav
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11051
AB  - Adolescence is a developmental stage characterized by impaired fear extinction learning, which is a significant contributing factor for the high incidence of fearrelated disorders observed across this period. Ketamine is a noncompetitive N-methyl D-aspartate receptor antagonist that targets glutamatergic transmission and mammalian target of rapamycin (mTOR) signaling pathway, synaptic plasticity mediators known to be involved in fear extinction processes. Therefore, we aimed to explore ketamine’s potential to boost fear extinction of adolescent males, as well as to identify the associated molecular mechanisms. Adolescent male mice (C57BL/6) received an i.p. ketamine injection (10 mg/kg) 1h prior to each cued fear extinction session for 4 consecutive days. Protein expression levels of synaptic plasticity markers in hippocampal synaptosomal fractions were subsequently detected by Western blot analysis. Our results revealed that ketamine significantly improved overall fear extinction learning, as well as extinction memory consolidation/retention. Our data also showed that ketamine upregulated protein kinase B (Akt), mTOR and glutamate receptor 1 (GluR1) protein levels in the hippocampus. Interestingly, we detected no changes in the levels of extracellular signal-regulated kinase 1/2. These results suggest that ketamine ameliorates longterm fear extinction of adolescent males via hippocampal Akt-mTOR-GluR1 signaling, highlighting this pathway as an important therapeutic target for improving extinction learning in the adolescent population.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - Ketamine ameliorates fear extinction learning in adolescent males via hippocampal mTOR signaling
SP  - 82
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11051
ER  - 

@conference{
author = "Glavonić, Emilija and Aleksić, Minja and Francija, Ester and Mitić, Miloš and Lukić, Iva and Ivković, Sanja and Adžić, Miroslav",
year = "2023",
abstract = "Adolescence is a developmental stage characterized by impaired fear extinction learning, which is a significant contributing factor for the high incidence of fearrelated disorders observed across this period. Ketamine is a noncompetitive N-methyl D-aspartate receptor antagonist that targets glutamatergic transmission and mammalian target of rapamycin (mTOR) signaling pathway, synaptic plasticity mediators known to be involved in fear extinction processes. Therefore, we aimed to explore ketamine’s potential to boost fear extinction of adolescent males, as well as to identify the associated molecular mechanisms. Adolescent male mice (C57BL/6) received an i.p. ketamine injection (10 mg/kg) 1h prior to each cued fear extinction session for 4 consecutive days. Protein expression levels of synaptic plasticity markers in hippocampal synaptosomal fractions were subsequently detected by Western blot analysis. Our results revealed that ketamine significantly improved overall fear extinction learning, as well as extinction memory consolidation/retention. Our data also showed that ketamine upregulated protein kinase B (Akt), mTOR and glutamate receptor 1 (GluR1) protein levels in the hippocampus. Interestingly, we detected no changes in the levels of extracellular signal-regulated kinase 1/2. These results suggest that ketamine ameliorates longterm fear extinction of adolescent males via hippocampal Akt-mTOR-GluR1 signaling, highlighting this pathway as an important therapeutic target for improving extinction learning in the adolescent population.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "Ketamine ameliorates fear extinction learning in adolescent males via hippocampal mTOR signaling",
pages = "82",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11051"
}

Glavonić, E., Aleksić, M., Francija, E., Mitić, M., Lukić, I., Ivković, S.,& Adžić, M.. (2023). Ketamine ameliorates fear extinction learning in adolescent males via hippocampal mTOR signaling. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neuroscience Society., 82.
https://hdl.handle.net/21.15107/rcub_vinar_11051

Glavonić E, Aleksić M, Francija E, Mitić M, Lukić I, Ivković S, Adžić M. Ketamine ameliorates fear extinction learning in adolescent males via hippocampal mTOR signaling. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:82.
https://hdl.handle.net/21.15107/rcub_vinar_11051 .

Glavonić, Emilija, Aleksić, Minja, Francija, Ester, Mitić, Miloš, Lukić, Iva, Ivković, Sanja, Adžić, Miroslav, "Ketamine ameliorates fear extinction learning in adolescent males via hippocampal mTOR signaling" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):82,
https://hdl.handle.net/21.15107/rcub_vinar_11051 .

TY  - CONF
AU  - Lukić, Iva
AU  - Mitić, Miloš
AU  - Pajović, Milica
AU  - Glavonić, Emilija
AU  - Živanović, Ana
AU  - Aleksić, Minja
AU  - Ivković, Sanja
AU  - Elliot, Evan
AU  - Adžić, Miroslav
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11045
AB  - There is accumulating evidence demonstrating effects of gastrointestinal microbiota on brain function and behavior, including depressive behavior. We have demonstrated that antidepressants, the main drugs used for alleviating depression, affect gut microbiota composition as well, and in this way partly contribute to improvement of depressive symptoms. Specifically, our results showed that several types of antidepressants reduced abundance of bacterial genera Ruminococcus, while supplementation with R. flavefaciens diminished antidepressant-induced decrease of depressive behavior. Treatment with R. flavefaciens affected cortical gene networks, up-regulating genes involved in mitochondrial oxidative phosphorylation, while down-regulating genes involved in neuronal plasticity, suggesting a mechanism for microbial regulation of antidepressant treatment efficiency. In further studies, we are aiming to delineate the role of gut microbiota in conveying the long-term effects of adolescent stress on development of anxiety and depressive behavior.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - The role of gut microbiota in depressive behavior and the effects of antidepressants
SP  - 44
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11045
ER  - 

@conference{
author = "Lukić, Iva and Mitić, Miloš and Pajović, Milica and Glavonić, Emilija and Živanović, Ana and Aleksić, Minja and Ivković, Sanja and Elliot, Evan and Adžić, Miroslav",
year = "2023",
abstract = "There is accumulating evidence demonstrating effects of gastrointestinal microbiota on brain function and behavior, including depressive behavior. We have demonstrated that antidepressants, the main drugs used for alleviating depression, affect gut microbiota composition as well, and in this way partly contribute to improvement of depressive symptoms. Specifically, our results showed that several types of antidepressants reduced abundance of bacterial genera Ruminococcus, while supplementation with R. flavefaciens diminished antidepressant-induced decrease of depressive behavior. Treatment with R. flavefaciens affected cortical gene networks, up-regulating genes involved in mitochondrial oxidative phosphorylation, while down-regulating genes involved in neuronal plasticity, suggesting a mechanism for microbial regulation of antidepressant treatment efficiency. In further studies, we are aiming to delineate the role of gut microbiota in conveying the long-term effects of adolescent stress on development of anxiety and depressive behavior.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "The role of gut microbiota in depressive behavior and the effects of antidepressants",
pages = "44",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11045"
}

Lukić, I., Mitić, M., Pajović, M., Glavonić, E., Živanović, A., Aleksić, M., Ivković, S., Elliot, E.,& Adžić, M.. (2023). The role of gut microbiota in depressive behavior and the effects of antidepressants. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neuroscience Society., 44.
https://hdl.handle.net/21.15107/rcub_vinar_11045

Lukić I, Mitić M, Pajović M, Glavonić E, Živanović A, Aleksić M, Ivković S, Elliot E, Adžić M. The role of gut microbiota in depressive behavior and the effects of antidepressants. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:44.
https://hdl.handle.net/21.15107/rcub_vinar_11045 .

Lukić, Iva, Mitić, Miloš, Pajović, Milica, Glavonić, Emilija, Živanović, Ana, Aleksić, Minja, Ivković, Sanja, Elliot, Evan, Adžić, Miroslav, "The role of gut microbiota in depressive behavior and the effects of antidepressants" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):44,
https://hdl.handle.net/21.15107/rcub_vinar_11045 .

TY  - CONF
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Glavonić, Emilija
AU  - Živanović, Ana
AU  - Mijović, Milica
AU  - Ivković, Sanja
AU  - Adžić, Miroslav
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11054
AB  - Adolescence is a critical period for neurodevelopment, and exposure to chronic stress during this stage can have long-lasting effects on physiological systems and mental health, particularly on depression. Recent studies report that stress affects the gutbrain axis, leading to changes in gut morphology and motility, nutrient absorption, and gut microbiome, which can be associated with development of depression. We investigated the impact of chronic unpredictable stress (CUS) in adolescence on depressive-like behavior and colon in adult mice. Male C57BL/6 mice were exposed to CUS, including different daily stressors such as social isolation, forced swim, and restraint stress, and others, during postnatal days 28-40. Control mice were housed under standard conditions. Behavioral assessments were conducted during adulthood (postnatal day 70), to evaluate depressive-like behavior. Alterations in mice colon were assessed by histopathological analysis. Our results revealed that mice exposed to CUS during adolescence have disrupted colon, including loss of colonic crypts and significantly increased presence of mucosa and submucosa in respect to controls. Changes in colon were associated with increased depressive-like behavior in CUS-mice compared to control mice. These findings suggest that CUS experienced in adolescence can disrupt colon morphology that is associated with depressive phenotype in adult mice, highlighting the importance of understanding the long-term consequences of chronic stress during this critical period of development as a potential risk for development of depression. Further research is needed to elucidate the underlying mechanisms and potential therapeutic interventions to mitigate the effects of stress on mental health and gut function
PB  - Belgrade : Serbian Neurocardiological Society
C3  - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
T1  - Chronic unpredictable stress in adolescence causes disruption of colon morphology that is associated with depressive phenotype in adult mice
SP  - 85
UR  - https://hdl.handle.net/21.15107/rcub_vinar_11054
ER  - 

@conference{
author = "Mitić, Miloš and Lukić, Iva and Glavonić, Emilija and Živanović, Ana and Mijović, Milica and Ivković, Sanja and Adžić, Miroslav",
year = "2023",
abstract = "Adolescence is a critical period for neurodevelopment, and exposure to chronic stress during this stage can have long-lasting effects on physiological systems and mental health, particularly on depression. Recent studies report that stress affects the gutbrain axis, leading to changes in gut morphology and motility, nutrient absorption, and gut microbiome, which can be associated with development of depression. We investigated the impact of chronic unpredictable stress (CUS) in adolescence on depressive-like behavior and colon in adult mice. Male C57BL/6 mice were exposed to CUS, including different daily stressors such as social isolation, forced swim, and restraint stress, and others, during postnatal days 28-40. Control mice were housed under standard conditions. Behavioral assessments were conducted during adulthood (postnatal day 70), to evaluate depressive-like behavior. Alterations in mice colon were assessed by histopathological analysis. Our results revealed that mice exposed to CUS during adolescence have disrupted colon, including loss of colonic crypts and significantly increased presence of mucosa and submucosa in respect to controls. Changes in colon were associated with increased depressive-like behavior in CUS-mice compared to control mice. These findings suggest that CUS experienced in adolescence can disrupt colon morphology that is associated with depressive phenotype in adult mice, highlighting the importance of understanding the long-term consequences of chronic stress during this critical period of development as a potential risk for development of depression. Further research is needed to elucidate the underlying mechanisms and potential therapeutic interventions to mitigate the effects of stress on mental health and gut function",
publisher = "Belgrade : Serbian Neurocardiological Society",
journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade",
title = "Chronic unpredictable stress in adolescence causes disruption of colon morphology that is associated with depressive phenotype in adult mice",
pages = "85",
url = "https://hdl.handle.net/21.15107/rcub_vinar_11054"
}

Mitić, M., Lukić, I., Glavonić, E., Živanović, A., Mijović, M., Ivković, S.,& Adžić, M.. (2023). Chronic unpredictable stress in adolescence causes disruption of colon morphology that is associated with depressive phenotype in adult mice. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade
Belgrade : Serbian Neurocardiological Society., 85.
https://hdl.handle.net/21.15107/rcub_vinar_11054

Mitić M, Lukić I, Glavonić E, Živanović A, Mijović M, Ivković S, Adžić M. Chronic unpredictable stress in adolescence causes disruption of colon morphology that is associated with depressive phenotype in adult mice. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:85.
https://hdl.handle.net/21.15107/rcub_vinar_11054 .

Mitić, Miloš, Lukić, Iva, Glavonić, Emilija, Živanović, Ana, Mijović, Milica, Ivković, Sanja, Adžić, Miroslav, "Chronic unpredictable stress in adolescence causes disruption of colon morphology that is associated with depressive phenotype in adult mice" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):85,
https://hdl.handle.net/21.15107/rcub_vinar_11054 .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Lukić, Iva
AU  - Mitić, Miloš
AU  - Glavonić, Emilija
AU  - Dragićević, Nina
AU  - Ivković, Sanja
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11044
AB  - Major depressive disorder (MDD) afflicts approximately 5 % of the world population, and about 30–50 % of patients who receive classical antidepressant medications do not achieve complete remission (treatment resistant depressive patients). Emerging evidence suggests that targeting opioid receptors mu (MOP), kappa (KOP), delta (DOP), and the nociceptin/orphanin FQ receptor (NOP) may yield effective therapeutics for stress-related psychiatric disorders. As depression and pain exhibit significant overlap in their clinical manifestations and molecular mechanisms involved, it is not a surprise that opioids, historically used to alleviate pain, emerged as promising and effective therapeutic options in the treatment of depression. The opioid signaling is dysregulated in depression and numerous preclinical studies and clinical trials strongly suggest that opioid modulation can serve as either an adjuvant or even an alternative to classical monoaminergic antidepressants. Importantly, some classical antidepressants require the opioid receptor modulation to exert their antidepressant effects. Finally, ketamine, a well-known anesthetic whose extremely efficient antidepressant effects were recently discovered, was shown to mediate its antidepressant effects via the endogenous opioid system. Thus, although opioid system modulation is a promising therapeutical venue in the treatment of depression further research is warranted to fully understand the benefits and weaknesses of such approach.
T2  - Life Sciences
T2  - Life SciencesLife Sciences
T1  - Contribution of the opioid system to depression and to the therapeutic effects of classical antidepressants and ketamine
VL  - 326
SP  - 121803
DO  - 10.1016/j.lfs.2023.121803
ER  - 

@article{
author = "Adžić, Miroslav and Lukić, Iva and Mitić, Miloš and Glavonić, Emilija and Dragićević, Nina and Ivković, Sanja",
year = "2023",
abstract = "Major depressive disorder (MDD) afflicts approximately 5 % of the world population, and about 30–50 % of patients who receive classical antidepressant medications do not achieve complete remission (treatment resistant depressive patients). Emerging evidence suggests that targeting opioid receptors mu (MOP), kappa (KOP), delta (DOP), and the nociceptin/orphanin FQ receptor (NOP) may yield effective therapeutics for stress-related psychiatric disorders. As depression and pain exhibit significant overlap in their clinical manifestations and molecular mechanisms involved, it is not a surprise that opioids, historically used to alleviate pain, emerged as promising and effective therapeutic options in the treatment of depression. The opioid signaling is dysregulated in depression and numerous preclinical studies and clinical trials strongly suggest that opioid modulation can serve as either an adjuvant or even an alternative to classical monoaminergic antidepressants. Importantly, some classical antidepressants require the opioid receptor modulation to exert their antidepressant effects. Finally, ketamine, a well-known anesthetic whose extremely efficient antidepressant effects were recently discovered, was shown to mediate its antidepressant effects via the endogenous opioid system. Thus, although opioid system modulation is a promising therapeutical venue in the treatment of depression further research is warranted to fully understand the benefits and weaknesses of such approach.",
journal = "Life Sciences, Life SciencesLife Sciences",
title = "Contribution of the opioid system to depression and to the therapeutic effects of classical antidepressants and ketamine",
volume = "326",
pages = "121803",
doi = "10.1016/j.lfs.2023.121803"
}

Adžić, M., Lukić, I., Mitić, M., Glavonić, E., Dragićević, N.,& Ivković, S.. (2023). Contribution of the opioid system to depression and to the therapeutic effects of classical antidepressants and ketamine. in Life Sciences, 326, 121803.
https://doi.org/10.1016/j.lfs.2023.121803

Adžić M, Lukić I, Mitić M, Glavonić E, Dragićević N, Ivković S. Contribution of the opioid system to depression and to the therapeutic effects of classical antidepressants and ketamine. in Life Sciences. 2023;326:121803.
doi:10.1016/j.lfs.2023.121803 .

Adžić, Miroslav, Lukić, Iva, Mitić, Miloš, Glavonić, Emilija, Dragićević, Nina, Ivković, Sanja, "Contribution of the opioid system to depression and to the therapeutic effects of classical antidepressants and ketamine" in Life Sciences, 326 (2023):121803,
https://doi.org/10.1016/j.lfs.2023.121803 . .

TY  - JOUR
AU  - Lukić, Iva
AU  - Ivković, Sanja
AU  - Mitić, Miloš
AU  - Adžić, Miroslav
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10443
AB  - Clinical depression is a multifactorial disorder and one of the leading causes of disability worldwide. The alterations in tryptophan metabolism such as changes in the levels of serotonin, kynurenine, and kynurenine acid have been implicated in the etiology of depression for more than 50 years. In recent years, accumulated evidence has revealed that gut microbial communities, besides being essential players in various aspects of host physiology and brain functioning are also implicated in the etiology of depression, particularly through modulation of tryptophan metabolism. Therefore, the aim of this review is to summarize the evidence of the role of gut bacteria in disturbed tryptophan metabolism in depression. We summed up the effects of microbiota on serotonin, kynurenine, and indole pathway of tryptophan conversion relevant for understanding the pathogenesis of depressive behavior. Moreover, we reviewed data regarding the therapeutic effects of probiotics, particularly through the regulation of tryptophan metabolites. Taken together, these findings can open new possibilities for further improvement of treatments for depression based on the microbiota-mediated modulation of the tryptophan pathway.
T2  - Frontiers in Behavioral Neuroscience
T1  - Tryptophan metabolites in depression: Modulation by gut microbiota
VL  - 16
DO  - 10.3389/fnbeh.2022.987697
ER  - 

@article{
author = "Lukić, Iva and Ivković, Sanja and Mitić, Miloš and Adžić, Miroslav",
year = "2022",
abstract = "Clinical depression is a multifactorial disorder and one of the leading causes of disability worldwide. The alterations in tryptophan metabolism such as changes in the levels of serotonin, kynurenine, and kynurenine acid have been implicated in the etiology of depression for more than 50 years. In recent years, accumulated evidence has revealed that gut microbial communities, besides being essential players in various aspects of host physiology and brain functioning are also implicated in the etiology of depression, particularly through modulation of tryptophan metabolism. Therefore, the aim of this review is to summarize the evidence of the role of gut bacteria in disturbed tryptophan metabolism in depression. We summed up the effects of microbiota on serotonin, kynurenine, and indole pathway of tryptophan conversion relevant for understanding the pathogenesis of depressive behavior. Moreover, we reviewed data regarding the therapeutic effects of probiotics, particularly through the regulation of tryptophan metabolites. Taken together, these findings can open new possibilities for further improvement of treatments for depression based on the microbiota-mediated modulation of the tryptophan pathway.",
journal = "Frontiers in Behavioral Neuroscience",
title = "Tryptophan metabolites in depression: Modulation by gut microbiota",
volume = "16",
doi = "10.3389/fnbeh.2022.987697"
}

Lukić, I., Ivković, S., Mitić, M.,& Adžić, M.. (2022). Tryptophan metabolites in depression: Modulation by gut microbiota. in Frontiers in Behavioral Neuroscience, 16.
https://doi.org/10.3389/fnbeh.2022.987697

Lukić I, Ivković S, Mitić M, Adžić M. Tryptophan metabolites in depression: Modulation by gut microbiota. in Frontiers in Behavioral Neuroscience. 2022;16.
doi:10.3389/fnbeh.2022.987697 .

Lukić, Iva, Ivković, Sanja, Mitić, Miloš, Adžić, Miroslav, "Tryptophan metabolites in depression: Modulation by gut microbiota" in Frontiers in Behavioral Neuroscience, 16 (2022),
https://doi.org/10.3389/fnbeh.2022.987697 . .

TY  - JOUR
AU  - Francija, Ester
AU  - Lukić, Iva
AU  - Petrović, Zorica
AU  - Brkić, Željka
AU  - Mitić, Miloš
AU  - Radulović, Jelena
AU  - Adžić, Miroslav
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10580
AB  - Inflammation plays a key role in the pathogenesis of the major depressive disorder. Namely, neuroinflammation can induce the production of neuroactive metabolites that interfere with N-methyl-D-aspartate receptors (NMDAR)-mediated glutamatergic neurotransmission and contribute to depressive-like behaviour. On the other hand, mammalian target of rapamycin (mTOR) activity with synaptogenic effects is the main mediator of antidepressant effects of several potent NMDAR antagonists. In this study, we investigated the specific role of GluN2A subunits of NMDAR on the activity of mTOR signaling and behaviour in lipopolysaccharide (LPS)-induces model of depression. The results showed that mice lacking GluN2A subunit did not display depressive-like behavior after the immune challenge, opposite to LPS-treated wild-type mice. Specifically, in GluN2A knockout mice, we estimated the activity of the mTOR pathway in the hippocampus and prefrontal cortex (PFC) by measuring synaptic levels of upstream regulators (p-Akt, p-ERK, and p-GSK3β) and downstream effectors (p-mTOR, and p-p70S6K) of mTOR activity. In addition, we assessed the changes in the levels of two important synaptic markers, GluA1 and PSD-95. Contrary to downregulated mTOR signaling and decreased synaptic markers in LPS-treated wild-type animals, the resilience of GluN2A KO mice to depressive-like behaviour was paralleled with sustained mTOR signaling activity synaptic stability in hippocampus and PFC. Finally, we disclosed that resistance of GluN2A knockouts to LPS-induced depressive-like behavior was ERK-dependent. These findings demonstrate that GluN2A-ERK-mTOR signaling is a vulnerability factor of inflammation-related depressive behaviour, making this signaling pathway the promising target for developing novel antidepressants.
T2  - Behavioural Brain Research
T1  - GluN2A-ERK-mTOR pathway confers a vulnerability to LPS-induced depressive-like behaviour
VL  - 417
SP  - 113625
DO  - 10.1016/j.bbr.2021.113625
ER  - 

@article{
author = "Francija, Ester and Lukić, Iva and Petrović, Zorica and Brkić, Željka and Mitić, Miloš and Radulović, Jelena and Adžić, Miroslav",
year = "2022",
abstract = "Inflammation plays a key role in the pathogenesis of the major depressive disorder. Namely, neuroinflammation can induce the production of neuroactive metabolites that interfere with N-methyl-D-aspartate receptors (NMDAR)-mediated glutamatergic neurotransmission and contribute to depressive-like behaviour. On the other hand, mammalian target of rapamycin (mTOR) activity with synaptogenic effects is the main mediator of antidepressant effects of several potent NMDAR antagonists. In this study, we investigated the specific role of GluN2A subunits of NMDAR on the activity of mTOR signaling and behaviour in lipopolysaccharide (LPS)-induces model of depression. The results showed that mice lacking GluN2A subunit did not display depressive-like behavior after the immune challenge, opposite to LPS-treated wild-type mice. Specifically, in GluN2A knockout mice, we estimated the activity of the mTOR pathway in the hippocampus and prefrontal cortex (PFC) by measuring synaptic levels of upstream regulators (p-Akt, p-ERK, and p-GSK3β) and downstream effectors (p-mTOR, and p-p70S6K) of mTOR activity. In addition, we assessed the changes in the levels of two important synaptic markers, GluA1 and PSD-95. Contrary to downregulated mTOR signaling and decreased synaptic markers in LPS-treated wild-type animals, the resilience of GluN2A KO mice to depressive-like behaviour was paralleled with sustained mTOR signaling activity synaptic stability in hippocampus and PFC. Finally, we disclosed that resistance of GluN2A knockouts to LPS-induced depressive-like behavior was ERK-dependent. These findings demonstrate that GluN2A-ERK-mTOR signaling is a vulnerability factor of inflammation-related depressive behaviour, making this signaling pathway the promising target for developing novel antidepressants.",
journal = "Behavioural Brain Research",
title = "GluN2A-ERK-mTOR pathway confers a vulnerability to LPS-induced depressive-like behaviour",
volume = "417",
pages = "113625",
doi = "10.1016/j.bbr.2021.113625"
}

Francija, E., Lukić, I., Petrović, Z., Brkić, Ž., Mitić, M., Radulović, J.,& Adžić, M.. (2022). GluN2A-ERK-mTOR pathway confers a vulnerability to LPS-induced depressive-like behaviour. in Behavioural Brain Research, 417, 113625.
https://doi.org/10.1016/j.bbr.2021.113625

Francija E, Lukić I, Petrović Z, Brkić Ž, Mitić M, Radulović J, Adžić M. GluN2A-ERK-mTOR pathway confers a vulnerability to LPS-induced depressive-like behaviour. in Behavioural Brain Research. 2022;417:113625.
doi:10.1016/j.bbr.2021.113625 .

Francija, Ester, Lukić, Iva, Petrović, Zorica, Brkić, Željka, Mitić, Miloš, Radulović, Jelena, Adžić, Miroslav, "GluN2A-ERK-mTOR pathway confers a vulnerability to LPS-induced depressive-like behaviour" in Behavioural Brain Research, 417 (2022):113625,
https://doi.org/10.1016/j.bbr.2021.113625 . .

TY  - JOUR
AU  - Aleksić, Minja
AU  - Brkić, Željka
AU  - Petrović, Zorica
AU  - Francija, Ester
AU  - Lukić, Iva
AU  - Adžić, Miroslav
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10579
AB  - Adolescent stress predisposes individuals to increased risk for anxiety and depression in adulthood. The stress response is mediated by the glucocorticoid receptor (GR) via regulation of GR-responsive genes involved in brain reaction to stress. Although dysregulation of GR in depression is well documented, this is the first study investigating the role of GRα isoforms in pathogenesis of depression. We exposed adolescent male and female C57BL/6J mice to chronic unpredictable stress (CUS) for 12 days starting at postnatal day 28 (PND28). Tests evaluating anxiety and depressive-like behaviors were performed at PND70. We analyzed corticosterone concentrations in serum, levels of GRα isoforms (95, 67, 50, 40, and 25 kDa), and mRNA levels of GR-responsive genes (GR, FKBP5, BDNF, and IL-1β) in the hippocampus and the prefrontal cortex (PFC). CUS increased anxiety and depressive-like behavior in adult animals of both sexes, but did not affect corticosterone serum levels, 95 and 67 kDa GR isoforms. However, the levels of shorter GRα isoforms (50, 40, and 25 kDa) were altered in adult mice underwent CUS, in sex- and brain structure–specific way. Changes in gene expression revealed that female depressive-like behavior could be related to increased levels of IL-1β in hippocampus and reduced BDNF levels in both hippocampus and PFC. However, in males, adolescent CUS increased expression of GR in adult hippocampus and BDNF in PFC. These findings suggest that adolescent stress altered levels of GRα isoforms, especially those with lower molecular weight, in sex- and tissue-specific ways, contributing to anxiety and depression in adult mice.
T2  - Journal of Neuroscience Research
T1  - Sex-specific contribution of glucocorticoid receptor alpha isoforms to anxiety and depressive-like behavior in mice
VL  - 100
IS  - 5
SP  - 1239
EP  - 1253
DO  - 10.1002/jnr.25032
ER  - 

@article{
author = "Aleksić, Minja and Brkić, Željka and Petrović, Zorica and Francija, Ester and Lukić, Iva and Adžić, Miroslav",
year = "2022",
abstract = "Adolescent stress predisposes individuals to increased risk for anxiety and depression in adulthood. The stress response is mediated by the glucocorticoid receptor (GR) via regulation of GR-responsive genes involved in brain reaction to stress. Although dysregulation of GR in depression is well documented, this is the first study investigating the role of GRα isoforms in pathogenesis of depression. We exposed adolescent male and female C57BL/6J mice to chronic unpredictable stress (CUS) for 12 days starting at postnatal day 28 (PND28). Tests evaluating anxiety and depressive-like behaviors were performed at PND70. We analyzed corticosterone concentrations in serum, levels of GRα isoforms (95, 67, 50, 40, and 25 kDa), and mRNA levels of GR-responsive genes (GR, FKBP5, BDNF, and IL-1β) in the hippocampus and the prefrontal cortex (PFC). CUS increased anxiety and depressive-like behavior in adult animals of both sexes, but did not affect corticosterone serum levels, 95 and 67 kDa GR isoforms. However, the levels of shorter GRα isoforms (50, 40, and 25 kDa) were altered in adult mice underwent CUS, in sex- and brain structure–specific way. Changes in gene expression revealed that female depressive-like behavior could be related to increased levels of IL-1β in hippocampus and reduced BDNF levels in both hippocampus and PFC. However, in males, adolescent CUS increased expression of GR in adult hippocampus and BDNF in PFC. These findings suggest that adolescent stress altered levels of GRα isoforms, especially those with lower molecular weight, in sex- and tissue-specific ways, contributing to anxiety and depression in adult mice.",
journal = "Journal of Neuroscience Research",
title = "Sex-specific contribution of glucocorticoid receptor alpha isoforms to anxiety and depressive-like behavior in mice",
volume = "100",
number = "5",
pages = "1239-1253",
doi = "10.1002/jnr.25032"
}

Aleksić, M., Brkić, Ž., Petrović, Z., Francija, E., Lukić, I.,& Adžić, M.. (2022). Sex-specific contribution of glucocorticoid receptor alpha isoforms to anxiety and depressive-like behavior in mice. in Journal of Neuroscience Research, 100(5), 1239-1253.
https://doi.org/10.1002/jnr.25032

Aleksić M, Brkić Ž, Petrović Z, Francija E, Lukić I, Adžić M. Sex-specific contribution of glucocorticoid receptor alpha isoforms to anxiety and depressive-like behavior in mice. in Journal of Neuroscience Research. 2022;100(5):1239-1253.
doi:10.1002/jnr.25032 .

Aleksić, Minja, Brkić, Željka, Petrović, Zorica, Francija, Ester, Lukić, Iva, Adžić, Miroslav, "Sex-specific contribution of glucocorticoid receptor alpha isoforms to anxiety and depressive-like behavior in mice" in Journal of Neuroscience Research, 100, no. 5 (2022):1239-1253,
https://doi.org/10.1002/jnr.25032 . .

TY  - JOUR
AU  - Mihaljević, Marina
AU  - Franić, Dušanka
AU  - Soldatović, Ivan A.
AU  - Lukić, Iva
AU  - Andrić-Petrović, Sanja
AU  - Mirjanić, Tijana
AU  - Stanković, Biljana
AU  - Žukić, Branka
AU  - Željić, Katarina
AU  - Gašić, Vladimir
AU  - Novaković, Ivana
AU  - Pavlović, Sonja
AU  - Adžić, Miroslav
AU  - Marić, Nađa P.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9748
AB  - Hypothalamic–pituitary–adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation. © 2021 Elsevier Ltd
T2  - Psychoneuroendocrinology
T1  - The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls
VL  - 128
SP  - 105205
DO  - 10.1016/j.psyneuen.2021.105205
ER  - 

@article{
author = "Mihaljević, Marina and Franić, Dušanka and Soldatović, Ivan A. and Lukić, Iva and Andrić-Petrović, Sanja and Mirjanić, Tijana and Stanković, Biljana and Žukić, Branka and Željić, Katarina and Gašić, Vladimir and Novaković, Ivana and Pavlović, Sonja and Adžić, Miroslav and Marić, Nađa P.",
year = "2021",
abstract = "Hypothalamic–pituitary–adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation. © 2021 Elsevier Ltd",
journal = "Psychoneuroendocrinology",
title = "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls",
volume = "128",
pages = "105205",
doi = "10.1016/j.psyneuen.2021.105205"
}

Mihaljević, M., Franić, D., Soldatović, I. A., Lukić, I., Andrić-Petrović, S., Mirjanić, T., Stanković, B., Žukić, B., Željić, K., Gašić, V., Novaković, I., Pavlović, S., Adžić, M.,& Marić, N. P.. (2021). The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology, 128, 105205.
https://doi.org/10.1016/j.psyneuen.2021.105205

Mihaljević M, Franić D, Soldatović IA, Lukić I, Andrić-Petrović S, Mirjanić T, Stanković B, Žukić B, Željić K, Gašić V, Novaković I, Pavlović S, Adžić M, Marić NP. The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology. 2021;128:105205.
doi:10.1016/j.psyneuen.2021.105205 .

Mihaljević, Marina, Franić, Dušanka, Soldatović, Ivan A., Lukić, Iva, Andrić-Petrović, Sanja, Mirjanić, Tijana, Stanković, Biljana, Žukić, Branka, Željić, Katarina, Gašić, Vladimir, Novaković, Ivana, Pavlović, Sonja, Adžić, Miroslav, Marić, Nađa P., "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls" in Psychoneuroendocrinology, 128 (2021):105205,
https://doi.org/10.1016/j.psyneuen.2021.105205 . .

TY  - CONF
AU  - Marić, Nađa
AU  - Mihaljević, Marina
AU  - Franić, Dušanka
AU  - Soldatovic, Ivan
AU  - Andrić, Sanja
AU  - Lukić, Iva
AU  - Mirjanic, Tijana
AU  - Stankovic, Biljana
AU  - Zukic, Branka
AU  - Dobricic, Valerija
AU  - Novaković, Ivana
AU  - Pavlović, Sonja
AU  - Adžić, Miroslav
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7156
C3  - Schizophrenia Bulletin
T1  - The Signature of Trauma in Psychosis: a Preliminary Genetic and Epigenetic Analyses of Fk506-Binding Protein 5 Regulation
VL  - 43
SP  - S66
EP  - S66
UR  - https://hdl.handle.net/21.15107/rcub_vinar_7156
ER  - 

@conference{
author = "Marić, Nađa and Mihaljević, Marina and Franić, Dušanka and Soldatovic, Ivan and Andrić, Sanja and Lukić, Iva and Mirjanic, Tijana and Stankovic, Biljana and Zukic, Branka and Dobricic, Valerija and Novaković, Ivana and Pavlović, Sonja and Adžić, Miroslav",
year = "2017",
journal = "Schizophrenia Bulletin",
title = "The Signature of Trauma in Psychosis: a Preliminary Genetic and Epigenetic Analyses of Fk506-Binding Protein 5 Regulation",
volume = "43",
pages = "S66-S66",
url = "https://hdl.handle.net/21.15107/rcub_vinar_7156"
}

Marić, N., Mihaljević, M., Franić, D., Soldatovic, I., Andrić, S., Lukić, I., Mirjanic, T., Stankovic, B., Zukic, B., Dobricic, V., Novaković, I., Pavlović, S.,& Adžić, M.. (2017). The Signature of Trauma in Psychosis: a Preliminary Genetic and Epigenetic Analyses of Fk506-Binding Protein 5 Regulation. in Schizophrenia Bulletin, 43, S66-S66.
https://hdl.handle.net/21.15107/rcub_vinar_7156

Marić N, Mihaljević M, Franić D, Soldatovic I, Andrić S, Lukić I, Mirjanic T, Stankovic B, Zukic B, Dobricic V, Novaković I, Pavlović S, Adžić M. The Signature of Trauma in Psychosis: a Preliminary Genetic and Epigenetic Analyses of Fk506-Binding Protein 5 Regulation. in Schizophrenia Bulletin. 2017;43:S66-S66.
https://hdl.handle.net/21.15107/rcub_vinar_7156 .

Marić, Nađa, Mihaljević, Marina, Franić, Dušanka, Soldatovic, Ivan, Andrić, Sanja, Lukić, Iva, Mirjanic, Tijana, Stankovic, Biljana, Zukic, Branka, Dobricic, Valerija, Novaković, Ivana, Pavlović, Sonja, Adžić, Miroslav, "The Signature of Trauma in Psychosis: a Preliminary Genetic and Epigenetic Analyses of Fk506-Binding Protein 5 Regulation" in Schizophrenia Bulletin, 43 (2017):S66-S66,
https://hdl.handle.net/21.15107/rcub_vinar_7156 .

TY  - JOUR
AU  - Mitić, Miloš
AU  - Brkić, Željka
AU  - Lukić, Iva
AU  - Adžić, Miroslav
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1695
AB  - Accumulating evidence strongly suggest that impaired glucocorticoid receptor (GR) signaling is involved in stress-related mood disorders, and nominate GR as a potential target for antidepressants (ADs). It is known that different classes of ADs affects the GR action via modifying its phosphorylation, while the mechanism through which ADs alter GR phosphorylation targeted by GSK3 beta, a kinase modulated via serotonin neurotransmission, are unclear. On this basis, we investigated whether GSK3 beta-GR signaling could be a convergence point of fluoxetine action on brain function and behavior, by examining its effect on GSK3 beta targeted-GR phosphorylation on threonine 171 (pGR171), and expression of GR-regulated genes in the hippocampus of female and male rats exposed to chronic isolation stress. Stress induced sex-specific GSK3 beta-targeted phosphorylation of pGR171 in the nucleus of the hippocampus of stressed animals. Namely, while in females stress triggered coupled action of GSK3 beta-pGR171 signaling, in males changes in pGR171 levels did not correspond to GSK3 beta activity. On the other hand, fluoxetine managed to up regulate this pathway in sex-unbiased manner. Furthermore, fluoxetine reverted stress-induced changes in most of the analyzed genes in males, CRH, 5-HT1a and p11, while in females its effect was limited to CRH. These data further suggest that pGR171 signaling affects cellular localization of GR in response to chronic stress and fluoxetine in both sexes. Collectively, our results describe a novel convergence point between GR signaling and GSK3 beta pathway in rat hippocampus in response to stress and fluoxetine in both sexes and its involvement in fluoxetine-regulated brain function in males.
T2  - Behavioural Brain Research
T1  - Convergence of glycogen synthase kinase 3 beta and GR signaling in response to fluoxetine treatment in chronically stressed female and male rats
VL  - 333
SP  - 295
EP  - 303
DO  - 10.1016/j.bbr.2017.07.014
ER  - 

@article{
author = "Mitić, Miloš and Brkić, Željka and Lukić, Iva and Adžić, Miroslav",
year = "2017",
abstract = "Accumulating evidence strongly suggest that impaired glucocorticoid receptor (GR) signaling is involved in stress-related mood disorders, and nominate GR as a potential target for antidepressants (ADs). It is known that different classes of ADs affects the GR action via modifying its phosphorylation, while the mechanism through which ADs alter GR phosphorylation targeted by GSK3 beta, a kinase modulated via serotonin neurotransmission, are unclear. On this basis, we investigated whether GSK3 beta-GR signaling could be a convergence point of fluoxetine action on brain function and behavior, by examining its effect on GSK3 beta targeted-GR phosphorylation on threonine 171 (pGR171), and expression of GR-regulated genes in the hippocampus of female and male rats exposed to chronic isolation stress. Stress induced sex-specific GSK3 beta-targeted phosphorylation of pGR171 in the nucleus of the hippocampus of stressed animals. Namely, while in females stress triggered coupled action of GSK3 beta-pGR171 signaling, in males changes in pGR171 levels did not correspond to GSK3 beta activity. On the other hand, fluoxetine managed to up regulate this pathway in sex-unbiased manner. Furthermore, fluoxetine reverted stress-induced changes in most of the analyzed genes in males, CRH, 5-HT1a and p11, while in females its effect was limited to CRH. These data further suggest that pGR171 signaling affects cellular localization of GR in response to chronic stress and fluoxetine in both sexes. Collectively, our results describe a novel convergence point between GR signaling and GSK3 beta pathway in rat hippocampus in response to stress and fluoxetine in both sexes and its involvement in fluoxetine-regulated brain function in males.",
journal = "Behavioural Brain Research",
title = "Convergence of glycogen synthase kinase 3 beta and GR signaling in response to fluoxetine treatment in chronically stressed female and male rats",
volume = "333",
pages = "295-303",
doi = "10.1016/j.bbr.2017.07.014"
}

Mitić, M., Brkić, Ž., Lukić, I.,& Adžić, M.. (2017). Convergence of glycogen synthase kinase 3 beta and GR signaling in response to fluoxetine treatment in chronically stressed female and male rats. in Behavioural Brain Research, 333, 295-303.
https://doi.org/10.1016/j.bbr.2017.07.014

Mitić M, Brkić Ž, Lukić I, Adžić M. Convergence of glycogen synthase kinase 3 beta and GR signaling in response to fluoxetine treatment in chronically stressed female and male rats. in Behavioural Brain Research. 2017;333:295-303.
doi:10.1016/j.bbr.2017.07.014 .

Mitić, Miloš, Brkić, Željka, Lukić, Iva, Adžić, Miroslav, "Convergence of glycogen synthase kinase 3 beta and GR signaling in response to fluoxetine treatment in chronically stressed female and male rats" in Behavioural Brain Research, 333 (2017):295-303,
https://doi.org/10.1016/j.bbr.2017.07.014 . .

TY  - JOUR
AU  - Brkić, Željka
AU  - Francija, Ester
AU  - Petrović, Zorica D.
AU  - Franić, Dušanka
AU  - Lukić, Iva
AU  - Mitić, Miloš
AU  - Adžić, Miroslav
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1888
AB  - Inflammation plays a critical role in pathogenesis of depression and can affect the hypothalamic-pituitary-adrenal axis activity. Accordingly, in this study we investigated the role of hippocampal glucocorticoid receptor in mediating the effects of inflammation on behaviour of female and male Wistar rats. We studied the effects of lipopolysaccharide on the levels of glucocorticoid receptors and its co-chaperones FK506 binding protein 52 and FK506 binding protein 51, the levels of glucocorticoid receptor phospho-isoforms, pGR-232 and pGR-246, and glucocorticoid receptor up-stream kinases. In order to assess transcriptional activity of glucocorticoid receptor, we measured mRNA levels of several glucocorticoid receptor-regulated genes. We demonstrated that lipopolysaccharide induced depressive-like behaviour and elevated serum corticosterone in both sexes. However, it affected glucocorticoid receptor signalling in the nucleus of females and males differently-in females it elevated levels of glucocorticoid receptors, pGR-246 and FK506 binding protein 52, while in males it decreased levels of glucocorticoid receptor, both co-chaperons and pGR-246. Alterations in pGR-246 were associated with alterations of c-Jun N-terminal kinases. Altered nuclear levels of total glucocorticoid receptors and pGR-246 were accompanied by sex-specific reduction in brain-derived neurotrophic factor and cyclooxygenase-2 mRNA and sex-unspecific reduction in the expression of p11 and glucocorticoid receptor genes. These alterations may ultimately affect different glucocorticoid receptor-associated processes involved in depressive-like behaviour in males and females.
T2  - Journal of Psychopharmacology
T1  - Distinct modifications of hippocampal glucocorticoid receptor phosphorylation and FKBPs by lipopolysaccharide in depressive female and male rats
VL  - 31
IS  - 9
SP  - 1234
EP  - 1249
DO  - 10.1177/0269881117725914
ER  - 

@article{
author = "Brkić, Željka and Francija, Ester and Petrović, Zorica D. and Franić, Dušanka and Lukić, Iva and Mitić, Miloš and Adžić, Miroslav",
year = "2017",
abstract = "Inflammation plays a critical role in pathogenesis of depression and can affect the hypothalamic-pituitary-adrenal axis activity. Accordingly, in this study we investigated the role of hippocampal glucocorticoid receptor in mediating the effects of inflammation on behaviour of female and male Wistar rats. We studied the effects of lipopolysaccharide on the levels of glucocorticoid receptors and its co-chaperones FK506 binding protein 52 and FK506 binding protein 51, the levels of glucocorticoid receptor phospho-isoforms, pGR-232 and pGR-246, and glucocorticoid receptor up-stream kinases. In order to assess transcriptional activity of glucocorticoid receptor, we measured mRNA levels of several glucocorticoid receptor-regulated genes. We demonstrated that lipopolysaccharide induced depressive-like behaviour and elevated serum corticosterone in both sexes. However, it affected glucocorticoid receptor signalling in the nucleus of females and males differently-in females it elevated levels of glucocorticoid receptors, pGR-246 and FK506 binding protein 52, while in males it decreased levels of glucocorticoid receptor, both co-chaperons and pGR-246. Alterations in pGR-246 were associated with alterations of c-Jun N-terminal kinases. Altered nuclear levels of total glucocorticoid receptors and pGR-246 were accompanied by sex-specific reduction in brain-derived neurotrophic factor and cyclooxygenase-2 mRNA and sex-unspecific reduction in the expression of p11 and glucocorticoid receptor genes. These alterations may ultimately affect different glucocorticoid receptor-associated processes involved in depressive-like behaviour in males and females.",
journal = "Journal of Psychopharmacology",
title = "Distinct modifications of hippocampal glucocorticoid receptor phosphorylation and FKBPs by lipopolysaccharide in depressive female and male rats",
volume = "31",
number = "9",
pages = "1234-1249",
doi = "10.1177/0269881117725914"
}

Brkić, Ž., Francija, E., Petrović, Z. D., Franić, D., Lukić, I., Mitić, M.,& Adžić, M.. (2017). Distinct modifications of hippocampal glucocorticoid receptor phosphorylation and FKBPs by lipopolysaccharide in depressive female and male rats. in Journal of Psychopharmacology, 31(9), 1234-1249.
https://doi.org/10.1177/0269881117725914

Brkić Ž, Francija E, Petrović ZD, Franić D, Lukić I, Mitić M, Adžić M. Distinct modifications of hippocampal glucocorticoid receptor phosphorylation and FKBPs by lipopolysaccharide in depressive female and male rats. in Journal of Psychopharmacology. 2017;31(9):1234-1249.
doi:10.1177/0269881117725914 .

Brkić, Željka, Francija, Ester, Petrović, Zorica D., Franić, Dušanka, Lukić, Iva, Mitić, Miloš, Adžić, Miroslav, "Distinct modifications of hippocampal glucocorticoid receptor phosphorylation and FKBPs by lipopolysaccharide in depressive female and male rats" in Journal of Psychopharmacology, 31, no. 9 (2017):1234-1249,
https://doi.org/10.1177/0269881117725914 . .

TY  - JOUR
AU  - Đorđević, Jelena D.
AU  - Đorđević, Ana D.
AU  - Adžić, Miroslav
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Radojčić, Marija B.
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/270
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 and 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
VL  - 1602
SP  - 20
EP  - 31
DO  - 10.1016/j.brainres.2015.01.010
ER  - 

@article{
author = "Đorđević, Jelena D. and Đorđević, Ana D. and Adžić, Miroslav and Mitić, Miloš and Lukić, Iva and Radojčić, 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 and 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",
volume = "1602",
pages = "20-31",
doi = "10.1016/j.brainres.2015.01.010"
}

Đorđević, J. D., Đorđević, A. D., Adžić, M., Mitić, M., Lukić, I.,& Radojčić, M. B.. (2015). Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress. in Brain Research, 1602, 20-31.
https://doi.org/10.1016/j.brainres.2015.01.010

Đorđević JD, Đorđević AD, Adžić M, Mitić M, Lukić I, Radojčić MB. Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress. in Brain Research. 2015;1602:20-31.
doi:10.1016/j.brainres.2015.01.010 .

Đorđević, Jelena D., Đorđević, Ana D., Adžić, Miroslav, Mitić, Miloš, Lukić, Iva, Radojčić, Marija B., "Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress" in Brain Research, 1602 (2015):20-31,
https://doi.org/10.1016/j.brainres.2015.01.010 . .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Đorđević, Jelena D.
AU  - Mitić, Miloš
AU  - Brkić, Željka
AU  - Lukić, Iva
AU  - Radojčić, Marija
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/670
AB  - Peripheral inflammation induced by lipopolysaccharide (LPS) causes behavioural changes indicative for depression. The possible mechanisms involve the interference with neuroinflammatory, neuroendocrine, and neurotrophic processes. Apart from heterogeneity in the molecular background, sexual context may be another factor relevant to the manifestation of mood disturbances upon an immune challenge. We investigated sex-dependent effects of a 7-day LPS treatment of adult Wistar rats on depressive-like behaviour and their relation with hypothalamic neuroendocrine factor, corticotrophin-releasing hormone (CRH), proplastic brain-derived neurotropic factor (BDNF), pro-inflammatory cyclooxygenase-2 (COX-2) and nuclear factor kappa beta (NFkB). Also, their regulators, the glucocorticoid receptor (GR) and CCAAT enhancer-binding protein (C/EBP) beta were followed. LPS induced depressive-like behaviour in females was associated with the increased hypothalamic CRH and decreased BDNF, but not with COX-2. These changes were paralleled by an increase in nuclear GR, NFkB and 20 kDa C/EBP beta. LPS also altered behaviour in males and increased CRH expression, but in contrast to females, this was accompanied with the elevated COX-2, accumulation of cytosolic GR and elevated nuclear 38 kDa C/EBP beta and NFkB. In conclusion, depressive-like phenotype induced by LPS in both sexes emerges from similar HPA axis activation and sex-specific alterations of hypothalamic molecular signalling: in males it is related to compromised control of neuroinflamation connected with cytoplasmic GR retention, while in females it is related to diminished proplastic capacity of BDNF. Sex-dependent mechanisms by which inflammation alters hypothalamic processes and cause pathological behaviour in animals, could be operative in the treatment of depression-related brain inflammation. (C) 2015 Elsevier B.V. All rights reserved.
T2  - Behavioural Brain Research
T1  - The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-beta
VL  - 291
SP  - 130
EP  - 139
DO  - 10.1016/j.bbr.2015.05.029
ER  - 

@article{
author = "Adžić, Miroslav and Đorđević, Jelena D. and Mitić, Miloš and Brkić, Željka and Lukić, Iva and Radojčić, Marija",
year = "2015",
abstract = "Peripheral inflammation induced by lipopolysaccharide (LPS) causes behavioural changes indicative for depression. The possible mechanisms involve the interference with neuroinflammatory, neuroendocrine, and neurotrophic processes. Apart from heterogeneity in the molecular background, sexual context may be another factor relevant to the manifestation of mood disturbances upon an immune challenge. We investigated sex-dependent effects of a 7-day LPS treatment of adult Wistar rats on depressive-like behaviour and their relation with hypothalamic neuroendocrine factor, corticotrophin-releasing hormone (CRH), proplastic brain-derived neurotropic factor (BDNF), pro-inflammatory cyclooxygenase-2 (COX-2) and nuclear factor kappa beta (NFkB). Also, their regulators, the glucocorticoid receptor (GR) and CCAAT enhancer-binding protein (C/EBP) beta were followed. LPS induced depressive-like behaviour in females was associated with the increased hypothalamic CRH and decreased BDNF, but not with COX-2. These changes were paralleled by an increase in nuclear GR, NFkB and 20 kDa C/EBP beta. LPS also altered behaviour in males and increased CRH expression, but in contrast to females, this was accompanied with the elevated COX-2, accumulation of cytosolic GR and elevated nuclear 38 kDa C/EBP beta and NFkB. In conclusion, depressive-like phenotype induced by LPS in both sexes emerges from similar HPA axis activation and sex-specific alterations of hypothalamic molecular signalling: in males it is related to compromised control of neuroinflamation connected with cytoplasmic GR retention, while in females it is related to diminished proplastic capacity of BDNF. Sex-dependent mechanisms by which inflammation alters hypothalamic processes and cause pathological behaviour in animals, could be operative in the treatment of depression-related brain inflammation. (C) 2015 Elsevier B.V. All rights reserved.",
journal = "Behavioural Brain Research",
title = "The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-beta",
volume = "291",
pages = "130-139",
doi = "10.1016/j.bbr.2015.05.029"
}

Adžić, M., Đorđević, J. D., Mitić, M., Brkić, Ž., Lukić, I.,& Radojčić, M.. (2015). The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-beta. in Behavioural Brain Research, 291, 130-139.
https://doi.org/10.1016/j.bbr.2015.05.029

Adžić M, Đorđević JD, Mitić M, Brkić Ž, Lukić I, Radojčić M. The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-beta. in Behavioural Brain Research. 2015;291:130-139.
doi:10.1016/j.bbr.2015.05.029 .

Adžić, Miroslav, Đorđević, Jelena D., Mitić, Miloš, Brkić, Željka, Lukić, Iva, Radojčić, Marija, "The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-beta" in Behavioural Brain Research, 291 (2015):130-139,
https://doi.org/10.1016/j.bbr.2015.05.029 . .

TY  - JOUR
AU  - Jovičić, Milica J.
AU  - Lukić, Iva
AU  - Radojčić, Marija
AU  - Adžić, Miroslav
AU  - Marić, Nađa P.
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/723
AB  - Glucocorticoid resistance is a common finding in major depressive disorder. Increased glucocorticoid receptor (GR) phosphorylation at serine 226 is associated with increased glucocorticoid resistance. Previously we have demonstrated that depressed patients exhibit higher levels of GR phosphorylated at serine 226 compared to healthy controls. The enzyme that is involved in this specific GR phosphorylation is c-Jun N-terminal kinase (JNK). We propose that modulation of glucocorticoid phosphorylation at serine 226, by targeting JNK signaling pathway, could be a potential strategy for antidepressant treatment. We base this assumption on the results of previous research that examined GR phosphorylation and JNK signaling in animal models and human studies. We also discuss the potential challenges in targeting JNK signaling pathway in depression. (C) 2015 Elsevier Ltd. All rights reserved.
T2  - Medical Hypotheses
T1  - Modulation of c-Jun N-terminal kinase signaling and specific glucocorticoid receptor phosphorylation in the treatment of major depression
VL  - 85
IS  - 3
SP  - 291
EP  - 294
DO  - 10.1016/j.mehy.2015.05.015
ER  - 

@article{
author = "Jovičić, Milica J. and Lukić, Iva and Radojčić, Marija and Adžić, Miroslav and Marić, Nađa P.",
year = "2015",
abstract = "Glucocorticoid resistance is a common finding in major depressive disorder. Increased glucocorticoid receptor (GR) phosphorylation at serine 226 is associated with increased glucocorticoid resistance. Previously we have demonstrated that depressed patients exhibit higher levels of GR phosphorylated at serine 226 compared to healthy controls. The enzyme that is involved in this specific GR phosphorylation is c-Jun N-terminal kinase (JNK). We propose that modulation of glucocorticoid phosphorylation at serine 226, by targeting JNK signaling pathway, could be a potential strategy for antidepressant treatment. We base this assumption on the results of previous research that examined GR phosphorylation and JNK signaling in animal models and human studies. We also discuss the potential challenges in targeting JNK signaling pathway in depression. (C) 2015 Elsevier Ltd. All rights reserved.",
journal = "Medical Hypotheses",
title = "Modulation of c-Jun N-terminal kinase signaling and specific glucocorticoid receptor phosphorylation in the treatment of major depression",
volume = "85",
number = "3",
pages = "291-294",
doi = "10.1016/j.mehy.2015.05.015"
}

Jovičić, M. J., Lukić, I., Radojčić, M., Adžić, M.,& Marić, N. P.. (2015). Modulation of c-Jun N-terminal kinase signaling and specific glucocorticoid receptor phosphorylation in the treatment of major depression. in Medical Hypotheses, 85(3), 291-294.
https://doi.org/10.1016/j.mehy.2015.05.015

Jovičić MJ, Lukić I, Radojčić M, Adžić M, Marić NP. Modulation of c-Jun N-terminal kinase signaling and specific glucocorticoid receptor phosphorylation in the treatment of major depression. in Medical Hypotheses. 2015;85(3):291-294.
doi:10.1016/j.mehy.2015.05.015 .

Jovičić, Milica J., Lukić, Iva, Radojčić, Marija, Adžić, Miroslav, Marić, Nađa P., "Modulation of c-Jun N-terminal kinase signaling and specific glucocorticoid receptor phosphorylation in the treatment of major depression" in Medical Hypotheses, 85, no. 3 (2015):291-294,
https://doi.org/10.1016/j.mehy.2015.05.015 . .

TY  - CHAP
AU  - Adžić, Miroslav
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Đorđević, Jelena D.
AU  - Radojčić, Marija B.
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10585
AB  - Major depression is a very common and serious mood disorder characterized by heterogeneous etiopathology. Treatment of the disease usually involves the use of antidepressant medications whose basic mechanism is achieved via increasing synaptic levels of monoamine neurotransmitters in different brain regions affected by the disease. Currently used antidepressant medications display limited efficacy with a pronounced delay to onset of action, and they all provoke disturbing side effects. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, basic and clinical researches are devoted to studying the effects of antidepressants, particularly those most commonly used, selective serotonin reuptake inhibitors (SSRIs), on the complex signaling network that is known to be altered in depression. This includes the effects of antidepressants on the hypothalamic-pituitaryadrenal axis (HPA) activity, production of neurotrophins and regulation of neurogenesis, pro-inflammatory and anti-inflammatory cytokines, oxidative stress and mitochondrial functioning. Herein, we discuss the latest published data from animal and clinical studies that have examined the effects of different SSRIs on depression-related pathophysiological mechanisms. Special attention will be dedicated to gender-specific effects of SSRIs action and to their adverse effects. © 2015 by Nova Science Publishers, Inc. All rights reserved.
T2  - Fluoxetine: Pharmacology, Mechanisms of Action and Potential Side Effects
T1  - Role of fluoxetine on depression-related pathophysiological mechanisms
SP  - 227
EP  - 278
UR  - https://hdl.handle.net/21.15107/rcub_vinar_10585
ER  - 

@inbook{
author = "Adžić, Miroslav and Mitić, Miloš and Lukić, Iva and Đorđević, Jelena D. and Radojčić, Marija B.",
year = "2015",
abstract = "Major depression is a very common and serious mood disorder characterized by heterogeneous etiopathology. Treatment of the disease usually involves the use of antidepressant medications whose basic mechanism is achieved via increasing synaptic levels of monoamine neurotransmitters in different brain regions affected by the disease. Currently used antidepressant medications display limited efficacy with a pronounced delay to onset of action, and they all provoke disturbing side effects. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, basic and clinical researches are devoted to studying the effects of antidepressants, particularly those most commonly used, selective serotonin reuptake inhibitors (SSRIs), on the complex signaling network that is known to be altered in depression. This includes the effects of antidepressants on the hypothalamic-pituitaryadrenal axis (HPA) activity, production of neurotrophins and regulation of neurogenesis, pro-inflammatory and anti-inflammatory cytokines, oxidative stress and mitochondrial functioning. Herein, we discuss the latest published data from animal and clinical studies that have examined the effects of different SSRIs on depression-related pathophysiological mechanisms. Special attention will be dedicated to gender-specific effects of SSRIs action and to their adverse effects. © 2015 by Nova Science Publishers, Inc. All rights reserved.",
journal = "Fluoxetine: Pharmacology, Mechanisms of Action and Potential Side Effects",
booktitle = "Role of fluoxetine on depression-related pathophysiological mechanisms",
pages = "227-278",
url = "https://hdl.handle.net/21.15107/rcub_vinar_10585"
}

Adžić, M., Mitić, M., Lukić, I., Đorđević, J. D.,& Radojčić, M. B.. (2015). Role of fluoxetine on depression-related pathophysiological mechanisms. in Fluoxetine: Pharmacology, Mechanisms of Action and Potential Side Effects, 227-278.
https://hdl.handle.net/21.15107/rcub_vinar_10585

Adžić M, Mitić M, Lukić I, Đorđević JD, Radojčić MB. Role of fluoxetine on depression-related pathophysiological mechanisms. in Fluoxetine: Pharmacology, Mechanisms of Action and Potential Side Effects. 2015;:227-278.
https://hdl.handle.net/21.15107/rcub_vinar_10585 .

Adžić, Miroslav, Mitić, Miloš, Lukić, Iva, Đorđević, Jelena D., Radojčić, Marija B., "Role of fluoxetine on depression-related pathophysiological mechanisms" in Fluoxetine: Pharmacology, Mechanisms of Action and Potential Side Effects (2015):227-278,
https://hdl.handle.net/21.15107/rcub_vinar_10585 .

TY  - JOUR
AU  - Đorđević, Jelena D.
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Adžić, Miroslav
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/477
AB  - The early postnatal environment is critical for its capacity to influence adult behavior, and is associated with traits of altered physiological and neurobiological function and long-term predisposition to depression. Here we describe the delayed effects of maternal deprivation (MD) in male and female Wistar pups on their physical development and behavior in adulthood in tasks designed to explore depressive-like (forced swimming test, FST), and anxiety-like behaviors (elevated plus maze, EPM). We observed that MD led to reduced body weight in adulthood, anxiety-like traits in the EPM test and increased activity in the phases of the FST. Particularly, a consistent sexual dimorphism was observed in the responses to MD. A lower increase in body weight during maturation of MD rats was more pronounced in males than in females. MD anxiogenic effects were more pronounced in females, while in FST only MD males showed a marked increase in swimming activity followed by decreased immobility.
T2  - Archives of Biological Sciences
T1  - Maternal Deprivation of Rat Pups Reduces Body Weight and Alters Behavior in Adulthood in a Gender-Specific Manner
VL  - 67
IS  - 1
SP  - 131
EP  - 138
DO  - 10.2298/ABS141002015D
ER  - 

@article{
author = "Đorđević, Jelena D. and Mitić, Miloš and Lukić, Iva and Adžić, Miroslav",
year = "2015",
abstract = "The early postnatal environment is critical for its capacity to influence adult behavior, and is associated with traits of altered physiological and neurobiological function and long-term predisposition to depression. Here we describe the delayed effects of maternal deprivation (MD) in male and female Wistar pups on their physical development and behavior in adulthood in tasks designed to explore depressive-like (forced swimming test, FST), and anxiety-like behaviors (elevated plus maze, EPM). We observed that MD led to reduced body weight in adulthood, anxiety-like traits in the EPM test and increased activity in the phases of the FST. Particularly, a consistent sexual dimorphism was observed in the responses to MD. A lower increase in body weight during maturation of MD rats was more pronounced in males than in females. MD anxiogenic effects were more pronounced in females, while in FST only MD males showed a marked increase in swimming activity followed by decreased immobility.",
journal = "Archives of Biological Sciences",
title = "Maternal Deprivation of Rat Pups Reduces Body Weight and Alters Behavior in Adulthood in a Gender-Specific Manner",
volume = "67",
number = "1",
pages = "131-138",
doi = "10.2298/ABS141002015D"
}

Đorđević, J. D., Mitić, M., Lukić, I.,& Adžić, M.. (2015). Maternal Deprivation of Rat Pups Reduces Body Weight and Alters Behavior in Adulthood in a Gender-Specific Manner. in Archives of Biological Sciences, 67(1), 131-138.
https://doi.org/10.2298/ABS141002015D

Đorđević JD, Mitić M, Lukić I, Adžić M. Maternal Deprivation of Rat Pups Reduces Body Weight and Alters Behavior in Adulthood in a Gender-Specific Manner. in Archives of Biological Sciences. 2015;67(1):131-138.
doi:10.2298/ABS141002015D .

Đorđević, Jelena D., Mitić, Miloš, Lukić, Iva, Adžić, Miroslav, "Maternal Deprivation of Rat Pups Reduces Body Weight and Alters Behavior in Adulthood in a Gender-Specific Manner" in Archives of Biological Sciences, 67, no. 1 (2015):131-138,
https://doi.org/10.2298/ABS141002015D . .

TY  - JOUR
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Božović, Natalija
AU  - Đorđević, Jelena D.
AU  - Adžić, Miroslav
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/861
AB  - Considerable evidence shows an association of depression with the immune system and emphasizes the importance of gender in the etiology of the disease and the response to inflammatory stimuli. We examined the influence of immune-challenged systems on depressive-like behavior in female rats in the context of gonadal hormones. We used a neuroinflammatory model of depression elicited by lipopolysaccharide (LPS) administration on naive and ovariectomized (OVX) female rats, and examined the effects of estradiol (E2) and/or progesterone (P4) replacement therapy on animal behavior, as assessed by the forced swimming test (FST). We found that LPS and OVX increase immobility in the FST, while LPS also decreased body weight in naive female rats. Further, even though P4 application alone showed beneficial effects on the behavioral profile (it reduced immobility and increased climbing), supplementation of both hormones (E2 and P4) together to OVX rats failed to do so. When OVX rats were exposed to LPS-induced immune challenge, neither hormone individually nor their combination had any effect on immobility, however, their joint supplementation increased climbing behavior. In conclusion, our study confirmed that both LPS and OVX induced depressive-like behavior in female rats. Furthermore, our results potentiate P4 supplementation in relieving the depressive-like symptomatology in OVX rats, most likely through fine-tuning of different neurotransmitter systems. In the context of an activated immune system, the application of E2 and/or P4 does not provide any advantageous effects on depressive-like behavior.
T2  - Archives of Biological Sciences
T1  - Effects of Female Gonadal Hormones and Lps on Depressive-Like Behavior in Rats
VL  - 67
IS  - 3
SP  - 1025
EP  - 1032
DO  - 10.2298/ABS150130065M
ER  - 

@article{
author = "Mitić, Miloš and Lukić, Iva and Božović, Natalija and Đorđević, Jelena D. and Adžić, Miroslav",
year = "2015",
abstract = "Considerable evidence shows an association of depression with the immune system and emphasizes the importance of gender in the etiology of the disease and the response to inflammatory stimuli. We examined the influence of immune-challenged systems on depressive-like behavior in female rats in the context of gonadal hormones. We used a neuroinflammatory model of depression elicited by lipopolysaccharide (LPS) administration on naive and ovariectomized (OVX) female rats, and examined the effects of estradiol (E2) and/or progesterone (P4) replacement therapy on animal behavior, as assessed by the forced swimming test (FST). We found that LPS and OVX increase immobility in the FST, while LPS also decreased body weight in naive female rats. Further, even though P4 application alone showed beneficial effects on the behavioral profile (it reduced immobility and increased climbing), supplementation of both hormones (E2 and P4) together to OVX rats failed to do so. When OVX rats were exposed to LPS-induced immune challenge, neither hormone individually nor their combination had any effect on immobility, however, their joint supplementation increased climbing behavior. In conclusion, our study confirmed that both LPS and OVX induced depressive-like behavior in female rats. Furthermore, our results potentiate P4 supplementation in relieving the depressive-like symptomatology in OVX rats, most likely through fine-tuning of different neurotransmitter systems. In the context of an activated immune system, the application of E2 and/or P4 does not provide any advantageous effects on depressive-like behavior.",
journal = "Archives of Biological Sciences",
title = "Effects of Female Gonadal Hormones and Lps on Depressive-Like Behavior in Rats",
volume = "67",
number = "3",
pages = "1025-1032",
doi = "10.2298/ABS150130065M"
}

Mitić, M., Lukić, I., Božović, N., Đorđević, J. D.,& Adžić, M.. (2015). Effects of Female Gonadal Hormones and Lps on Depressive-Like Behavior in Rats. in Archives of Biological Sciences, 67(3), 1025-1032.
https://doi.org/10.2298/ABS150130065M

Mitić M, Lukić I, Božović N, Đorđević JD, Adžić M. Effects of Female Gonadal Hormones and Lps on Depressive-Like Behavior in Rats. in Archives of Biological Sciences. 2015;67(3):1025-1032.
doi:10.2298/ABS150130065M .

Mitić, Miloš, Lukić, Iva, Božović, Natalija, Đorđević, Jelena D., Adžić, Miroslav, "Effects of Female Gonadal Hormones and Lps on Depressive-Like Behavior in Rats" in Archives of Biological Sciences, 67, no. 3 (2015):1025-1032,
https://doi.org/10.2298/ABS150130065M . .

TY  - JOUR
AU  - Lukić, Iva
AU  - Mitić, Miloš
AU  - Soldatovic, Ivan
AU  - Jovičić, Milica
AU  - Marić, Nađa
AU  - Radulović, Jelena
AU  - Adžić, Miroslav
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/445
AB  - We have previously shown that patients with the major depressive disorder (MDD) exhibited elevated phosphorylation of the lymphocyte glucocorticoid receptor (GR) at serine 226 (S226). Here, we further analyse potential alterations of GR signalization in lymphocytes of MDD patients, i.e. the cytoplasmic/nuclear distribution of GR, levels of FK506-binding protein 5 (FKBP5) and glucocorticoid-induced leucine zipper (GILZ). The FKBP5 acts as an important regulator of GR activation, by decreasing ligand binding and impeding translocation of the receptor to the nucleus, while GILZ mediates glucocorticoid anti-inflammatory effects. Our result showed that the depressed patients had significantly higher GR levels in the cytoplasm compared to controls, which was accompanied by higher FKBP5 levels. Linear regression model demonstrated significantly higher correlation between FKBP5 and cytoplasmic GR than the presence of MDD itself or phosphorylation of nuclear GR at S226. There were no differences in the levels of GILZ isoforms. Therefore, the results suggest that accumulation of the GR in cytoplasm is related to the elevation of FKBP5, adding one more step in understanding altered GR signalling in lymphocytes, and potentially brain tissue, of MDD patients.
T2  - Journal of Molecular Neuroscience
T1  - Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients
VL  - 55
IS  - 4
SP  - 951
EP  - 958
DO  - 10.1007/s12031-014-0451-z
ER  - 

@article{
author = "Lukić, Iva and Mitić, Miloš and Soldatovic, Ivan and Jovičić, Milica and Marić, Nađa and Radulović, Jelena and Adžić, Miroslav",
year = "2015",
abstract = "We have previously shown that patients with the major depressive disorder (MDD) exhibited elevated phosphorylation of the lymphocyte glucocorticoid receptor (GR) at serine 226 (S226). Here, we further analyse potential alterations of GR signalization in lymphocytes of MDD patients, i.e. the cytoplasmic/nuclear distribution of GR, levels of FK506-binding protein 5 (FKBP5) and glucocorticoid-induced leucine zipper (GILZ). The FKBP5 acts as an important regulator of GR activation, by decreasing ligand binding and impeding translocation of the receptor to the nucleus, while GILZ mediates glucocorticoid anti-inflammatory effects. Our result showed that the depressed patients had significantly higher GR levels in the cytoplasm compared to controls, which was accompanied by higher FKBP5 levels. Linear regression model demonstrated significantly higher correlation between FKBP5 and cytoplasmic GR than the presence of MDD itself or phosphorylation of nuclear GR at S226. There were no differences in the levels of GILZ isoforms. Therefore, the results suggest that accumulation of the GR in cytoplasm is related to the elevation of FKBP5, adding one more step in understanding altered GR signalling in lymphocytes, and potentially brain tissue, of MDD patients.",
journal = "Journal of Molecular Neuroscience",
title = "Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients",
volume = "55",
number = "4",
pages = "951-958",
doi = "10.1007/s12031-014-0451-z"
}

Lukić, I., Mitić, M., Soldatovic, I., Jovičić, M., Marić, N., Radulović, J.,& Adžić, M.. (2015). Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients. in Journal of Molecular Neuroscience, 55(4), 951-958.
https://doi.org/10.1007/s12031-014-0451-z

Lukić I, Mitić M, Soldatovic I, Jovičić M, Marić N, Radulović J, Adžić M. Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients. in Journal of Molecular Neuroscience. 2015;55(4):951-958.
doi:10.1007/s12031-014-0451-z .

Lukić, Iva, Mitić, Miloš, Soldatovic, Ivan, Jovičić, Milica, Marić, Nađa, Radulović, Jelena, Adžić, Miroslav, "Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients" in Journal of Molecular Neuroscience, 55, no. 4 (2015):951-958,
https://doi.org/10.1007/s12031-014-0451-z . .

TY  - JOUR
AU  - Jovičić, Milica
AU  - Marić, Nađa P.
AU  - Soldatovic, Ivan
AU  - Lukić, Iva
AU  - Andrić, Sanja
AU  - Mihaljević, Marina
AU  - Pavlović, Zorana
AU  - Mitić, Miloš
AU  - Adžić, Miroslav
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/707
AB  - Objectives. To develop a structural equation model of negative affectivity (NA) that involves interaction of glucocorticoid receptor (GR) signaling, personality dimensions and recent stressful life events. Methods. Seventy participants -35 diagnosed with major depression and 35 healthy controls, were enrolled in the study. Morning plasma cortisol levels were determined by chemiluminescent immunometric assays. Molecular parameters (total nuclear and cytoplasmatic GR, nuclear GR phosphorylated at serine 211 (pGR-211) and at serine 226 (pGR-226) and cytoplasmic FKBP51) were analysed from peripheral blood lymphocytes by Western blot. NA, personality dimensions and stressful life events were assessed by self-report instruments. Results. GR signalling parameters had direct independent effect on measures of NA, with pGR-226 levels showing the strongest correlation, followed by FKBP51 and pGR-211 levels. Neuroticism and extraversion also demonstrated strong independent effect on NA, while recent stressful events did not predict NA directly, but demonstrated a significant effect on personality dimensions. Cortisol, total nuclear GR and total cytoplasmatic GR levels were excluded from the model due to non-significant correlations with NA. Conclusions. Negative affectivity is a transdiagnostic factor in vulnerability to affective disorders and possible therapeutic target. Molecular signature of negative affectivity should incorporate GR phosphorylation with other known biological underpinnings.
T2  - World Journal of Biological Psychiatry
T1  - The role of glucocorticoid receptor phosphorylation in the model of negative affective states
VL  - 16
IS  - 5
SP  - 301
EP  - 311
DO  - 10.3109/15622975.2014.1000375
ER  - 

@article{
author = "Jovičić, Milica and Marić, Nađa P. and Soldatovic, Ivan and Lukić, Iva and Andrić, Sanja and Mihaljević, Marina and Pavlović, Zorana and Mitić, Miloš and Adžić, Miroslav",
year = "2015",
abstract = "Objectives. To develop a structural equation model of negative affectivity (NA) that involves interaction of glucocorticoid receptor (GR) signaling, personality dimensions and recent stressful life events. Methods. Seventy participants -35 diagnosed with major depression and 35 healthy controls, were enrolled in the study. Morning plasma cortisol levels were determined by chemiluminescent immunometric assays. Molecular parameters (total nuclear and cytoplasmatic GR, nuclear GR phosphorylated at serine 211 (pGR-211) and at serine 226 (pGR-226) and cytoplasmic FKBP51) were analysed from peripheral blood lymphocytes by Western blot. NA, personality dimensions and stressful life events were assessed by self-report instruments. Results. GR signalling parameters had direct independent effect on measures of NA, with pGR-226 levels showing the strongest correlation, followed by FKBP51 and pGR-211 levels. Neuroticism and extraversion also demonstrated strong independent effect on NA, while recent stressful events did not predict NA directly, but demonstrated a significant effect on personality dimensions. Cortisol, total nuclear GR and total cytoplasmatic GR levels were excluded from the model due to non-significant correlations with NA. Conclusions. Negative affectivity is a transdiagnostic factor in vulnerability to affective disorders and possible therapeutic target. Molecular signature of negative affectivity should incorporate GR phosphorylation with other known biological underpinnings.",
journal = "World Journal of Biological Psychiatry",
title = "The role of glucocorticoid receptor phosphorylation in the model of negative affective states",
volume = "16",
number = "5",
pages = "301-311",
doi = "10.3109/15622975.2014.1000375"
}

Jovičić, M., Marić, N. P., Soldatovic, I., Lukić, I., Andrić, S., Mihaljević, M., Pavlović, Z., Mitić, M.,& Adžić, M.. (2015). The role of glucocorticoid receptor phosphorylation in the model of negative affective states. in World Journal of Biological Psychiatry, 16(5), 301-311.
https://doi.org/10.3109/15622975.2014.1000375

Jovičić M, Marić NP, Soldatovic I, Lukić I, Andrić S, Mihaljević M, Pavlović Z, Mitić M, Adžić M. The role of glucocorticoid receptor phosphorylation in the model of negative affective states. in World Journal of Biological Psychiatry. 2015;16(5):301-311.
doi:10.3109/15622975.2014.1000375 .

Jovičić, Milica, Marić, Nađa P., Soldatovic, Ivan, Lukić, Iva, Andrić, Sanja, Mihaljević, Marina, Pavlović, Zorana, Mitić, Miloš, Adžić, Miroslav, "The role of glucocorticoid receptor phosphorylation in the model of negative affective states" in World Journal of Biological Psychiatry, 16, no. 5 (2015):301-311,
https://doi.org/10.3109/15622975.2014.1000375 . .

TY  - JOUR
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Božović, Natalija
AU  - Đorđević, Jelena D.
AU  - Adžić, Miroslav
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/367
AB  - A growing body of evidence indicates that mitogen-activated protein kinase (MAPK) participates in various stress-induced responses and is considered to be one of the pathophysiological mechanisms in depression. Surprisingly, the effect of antidepressants on MAPKs is almost unexplored, particularly from the perspective of sexes. The present study investigates the cytoplasm-nuclear distribution of MAPK family, c-Jun N-terminal kinases (JNKs) 1, 2 and 3; extracellular signal-regulated kinases (ERKs) 1 and 2; and p38 kinases, as well as their phosphoisoforms in the hippocampus of chronically stressed female and male rats and upon chronic fluoxetine treatment. Additionally, we analysed crosstalk between MAPK signalling and depressive-like behaviour which correlated with brain-derived neurotrophic factor (BDNF) expression. Our results emphasize a gender-specific and compartment-dependent response of MAPKs to stress and fluoxetine. In females, stress decreased pp38 and pJNK and induced cytosolic retention of pERKs which reduced all nuclear pMAPKs. These changes correlated with altered BDNF expression and behaviour. Similarly, in males, stress decreased pp38 but promoted nuclear translocation of pJNKs and pERKs. These stress alterations of pMAPKs in males were not associated with BDNF expression and depressive-like behaviour. Fluoxetine treatment in stressed females upregulated whole pMAPK signalling particularly those in nucleus which was followed with BDNF expression and normalization of behaviour. In stressed males, fluoxetine affected only cytosolic pJNKs, while nuclear pMAPK signalling and BDNF expression were unaffected even though fluoxetine normalized behaviour. Overall, our results suggest existence of gender-specific mechanism of fluoxetine on nuclear pMAPK/BDNF signalling and depressive-like behaviour and reinforce the antidepressant dogma that females and males respond differently to certain antidepressants.
T2  - Journal of Molecular Neuroscience
T1  - Fluoxetine Signature on Hippocampal MAPK Signalling in Sex-Dependent Manner
VL  - 55
IS  - 2
SP  - 335
EP  - 346
DO  - 10.1007/s12031-014-0328-1
ER  - 

@article{
author = "Mitić, Miloš and Lukić, Iva and Božović, Natalija and Đorđević, Jelena D. and Adžić, Miroslav",
year = "2015",
abstract = "A growing body of evidence indicates that mitogen-activated protein kinase (MAPK) participates in various stress-induced responses and is considered to be one of the pathophysiological mechanisms in depression. Surprisingly, the effect of antidepressants on MAPKs is almost unexplored, particularly from the perspective of sexes. The present study investigates the cytoplasm-nuclear distribution of MAPK family, c-Jun N-terminal kinases (JNKs) 1, 2 and 3; extracellular signal-regulated kinases (ERKs) 1 and 2; and p38 kinases, as well as their phosphoisoforms in the hippocampus of chronically stressed female and male rats and upon chronic fluoxetine treatment. Additionally, we analysed crosstalk between MAPK signalling and depressive-like behaviour which correlated with brain-derived neurotrophic factor (BDNF) expression. Our results emphasize a gender-specific and compartment-dependent response of MAPKs to stress and fluoxetine. In females, stress decreased pp38 and pJNK and induced cytosolic retention of pERKs which reduced all nuclear pMAPKs. These changes correlated with altered BDNF expression and behaviour. Similarly, in males, stress decreased pp38 but promoted nuclear translocation of pJNKs and pERKs. These stress alterations of pMAPKs in males were not associated with BDNF expression and depressive-like behaviour. Fluoxetine treatment in stressed females upregulated whole pMAPK signalling particularly those in nucleus which was followed with BDNF expression and normalization of behaviour. In stressed males, fluoxetine affected only cytosolic pJNKs, while nuclear pMAPK signalling and BDNF expression were unaffected even though fluoxetine normalized behaviour. Overall, our results suggest existence of gender-specific mechanism of fluoxetine on nuclear pMAPK/BDNF signalling and depressive-like behaviour and reinforce the antidepressant dogma that females and males respond differently to certain antidepressants.",
journal = "Journal of Molecular Neuroscience",
title = "Fluoxetine Signature on Hippocampal MAPK Signalling in Sex-Dependent Manner",
volume = "55",
number = "2",
pages = "335-346",
doi = "10.1007/s12031-014-0328-1"
}

Mitić, M., Lukić, I., Božović, N., Đorđević, J. D.,& Adžić, M.. (2015). Fluoxetine Signature on Hippocampal MAPK Signalling in Sex-Dependent Manner. in Journal of Molecular Neuroscience, 55(2), 335-346.
https://doi.org/10.1007/s12031-014-0328-1

Mitić M, Lukić I, Božović N, Đorđević JD, Adžić M. Fluoxetine Signature on Hippocampal MAPK Signalling in Sex-Dependent Manner. in Journal of Molecular Neuroscience. 2015;55(2):335-346.
doi:10.1007/s12031-014-0328-1 .

Mitić, Miloš, Lukić, Iva, Božović, Natalija, Đorđević, Jelena D., Adžić, Miroslav, "Fluoxetine Signature on Hippocampal MAPK Signalling in Sex-Dependent Manner" in Journal of Molecular Neuroscience, 55, no. 2 (2015):335-346,
https://doi.org/10.1007/s12031-014-0328-1 . .

TY  - JOUR
AU  - Lukić, Iva
AU  - Mitić, Miloš
AU  - Đorđević, Jelena D.
AU  - Tatalović, Nikola R.
AU  - Božović, Natalija
AU  - Soldatovic, Ivan
AU  - Mihaljević, Marina
AU  - Pavlović, Zorana
AU  - Radojčić, Marija
AU  - Marić, Nađa P.
AU  - Adžić, Miroslav
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/148
AB  - Background: Oxidative stress is reliably observed in major depressive disorder (MDD). However, molecular data on the principal cellular redox-sensitive transcriptional factors and the levels of their downstream-regulated antioxidant enzymes in MDD are scarce. Methods: In the peripheral blood mononuclear cells (PBMC) of subjects with a current episode of MDD (n = 30) and healthy controls (n = 35), we investigated alterations in the levels of redox-sensing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein, its inhibitor Keap1, and nuclear factor-kappa B (NF-kappa B), along with their cognate downstream effectors, the antioxidant enzymes (AOEs): manganese and copper zinc superoxide dismutase (MnSOD and CuZnSOD, respectively), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR). Results: MDD subjects exhibited higher levels of Nrf2 and its regulator Keap1, as well as NF-kappa B in the cytoplasm of PBMC compared to controls. This state was further reflected by increased levels of MnSOD, CuZnSOD and CAT proteins and by the lack of correlation between MnSOD and CAT, which could indicate impaired oxidative detoxification capacity in MDD patients. Moreover, increased levels of MnSOD, CuZnSOD and CAT in MDD patients positively correlated with levels of Nrf2, while increased levels of SODs were also positively related to NF-kappa B. There were no differences regarding the levels of GPx and GLR proteins, but the ratio of GLR/GPx was reduced, suggesting diminished capacity of GPx in antioxidative defence in PBMC of MDD subjects. Conclusion: These data provide evidence that MDD is characterized by up-regulation of redox-sensitive transcriptional factors (Nrf2 and NF-kappa B) and AOEs (MnSOD, CuZnSOD and CAT), indicating pro-oxidative state in the PBMC of MDD patients. (C) 2014 S. Karger AG, Basel
T2  - Neuropsychobiology
T1  - Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients
VL  - 70
IS  - 1
SP  - 1
EP  - 9
DO  - 10.1159/000362841
ER  - 

@article{
author = "Lukić, Iva and Mitić, Miloš and Đorđević, Jelena D. and Tatalović, Nikola R. and Božović, Natalija and Soldatovic, Ivan and Mihaljević, Marina and Pavlović, Zorana and Radojčić, Marija and Marić, Nađa P. and Adžić, Miroslav",
year = "2014",
abstract = "Background: Oxidative stress is reliably observed in major depressive disorder (MDD). However, molecular data on the principal cellular redox-sensitive transcriptional factors and the levels of their downstream-regulated antioxidant enzymes in MDD are scarce. Methods: In the peripheral blood mononuclear cells (PBMC) of subjects with a current episode of MDD (n = 30) and healthy controls (n = 35), we investigated alterations in the levels of redox-sensing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein, its inhibitor Keap1, and nuclear factor-kappa B (NF-kappa B), along with their cognate downstream effectors, the antioxidant enzymes (AOEs): manganese and copper zinc superoxide dismutase (MnSOD and CuZnSOD, respectively), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR). Results: MDD subjects exhibited higher levels of Nrf2 and its regulator Keap1, as well as NF-kappa B in the cytoplasm of PBMC compared to controls. This state was further reflected by increased levels of MnSOD, CuZnSOD and CAT proteins and by the lack of correlation between MnSOD and CAT, which could indicate impaired oxidative detoxification capacity in MDD patients. Moreover, increased levels of MnSOD, CuZnSOD and CAT in MDD patients positively correlated with levels of Nrf2, while increased levels of SODs were also positively related to NF-kappa B. There were no differences regarding the levels of GPx and GLR proteins, but the ratio of GLR/GPx was reduced, suggesting diminished capacity of GPx in antioxidative defence in PBMC of MDD subjects. Conclusion: These data provide evidence that MDD is characterized by up-regulation of redox-sensitive transcriptional factors (Nrf2 and NF-kappa B) and AOEs (MnSOD, CuZnSOD and CAT), indicating pro-oxidative state in the PBMC of MDD patients. (C) 2014 S. Karger AG, Basel",
journal = "Neuropsychobiology",
title = "Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients",
volume = "70",
number = "1",
pages = "1-9",
doi = "10.1159/000362841"
}

Lukić, I., Mitić, M., Đorđević, J. D., Tatalović, N. R., Božović, N., Soldatovic, I., Mihaljević, M., Pavlović, Z., Radojčić, M., Marić, N. P.,& Adžić, M.. (2014). Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients. in Neuropsychobiology, 70(1), 1-9.
https://doi.org/10.1159/000362841

Lukić I, Mitić M, Đorđević JD, Tatalović NR, Božović N, Soldatovic I, Mihaljević M, Pavlović Z, Radojčić M, Marić NP, Adžić M. Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients. in Neuropsychobiology. 2014;70(1):1-9.
doi:10.1159/000362841 .

Lukić, Iva, Mitić, Miloš, Đorđević, Jelena D., Tatalović, Nikola R., Božović, Natalija, Soldatovic, Ivan, Mihaljević, Marina, Pavlović, Zorana, Radojčić, Marija, Marić, Nađa P., Adžić, Miroslav, "Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients" in Neuropsychobiology, 70, no. 1 (2014):1-9,
https://doi.org/10.1159/000362841 . .

TY  - CONF
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Đorđević, Jelena D.
AU  - Adžić, Miroslav
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9190
AB  - In this study, we examined the influence of immunity on depressive-like
behavior in females in the context of gonadal hormones. We used
neuroinflammatory model of depression elicited by lipopolysaccharide
(LPS) administration on naïve and ovariectomozed (OVX) females and
examined the effects of estradiol (E2) and/or progesterone (P4) replacement
therapy on Wistar rat behavior. LPS induced depressive–like behavior in
both naïve and OVX females. Our behavioral data indicated that E2 and P4
applied alone had opposite effects compared to the E2/P4 combination. The
supplementation of both hormones attenuates detrimental effects of LPSinduced
inflammation, particularly through stimulation of noradrenergic
transmission. Overall immune challenge with LPS is able to induce
depressive-like behavior either of naïve or ovariectomized females,
particularly depending on ovarian hormones background.
PB  - Society of Physical Chemists of Serbia
C3  - Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry
T1  - Association of female gonadal hormones and immunity in depression
VL  - F-10-P
UR  - https://hdl.handle.net/21.15107/rcub_vinar_9190
ER  - 

@conference{
author = "Mitić, Miloš and Lukić, Iva and Đorđević, Jelena D. and Adžić, Miroslav",
year = "2014",
abstract = "In this study, we examined the influence of immunity on depressive-like
behavior in females in the context of gonadal hormones. We used
neuroinflammatory model of depression elicited by lipopolysaccharide
(LPS) administration on naïve and ovariectomozed (OVX) females and
examined the effects of estradiol (E2) and/or progesterone (P4) replacement
therapy on Wistar rat behavior. LPS induced depressive–like behavior in
both naïve and OVX females. Our behavioral data indicated that E2 and P4
applied alone had opposite effects compared to the E2/P4 combination. The
supplementation of both hormones attenuates detrimental effects of LPSinduced
inflammation, particularly through stimulation of noradrenergic
transmission. Overall immune challenge with LPS is able to induce
depressive-like behavior either of naïve or ovariectomized females,
particularly depending on ovarian hormones background.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry",
title = "Association of female gonadal hormones and immunity in depression",
volume = "F-10-P",
url = "https://hdl.handle.net/21.15107/rcub_vinar_9190"
}

Mitić, M., Lukić, I., Đorđević, J. D.,& Adžić, M.. (2014). Association of female gonadal hormones and immunity in depression. in Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry
Society of Physical Chemists of Serbia., F-10-P.
https://hdl.handle.net/21.15107/rcub_vinar_9190

Mitić M, Lukić I, Đorđević JD, Adžić M. Association of female gonadal hormones and immunity in depression. in Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry. 2014;F-10-P.
https://hdl.handle.net/21.15107/rcub_vinar_9190 .

Mitić, Miloš, Lukić, Iva, Đorđević, Jelena D., Adžić, Miroslav, "Association of female gonadal hormones and immunity in depression" in Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, F-10-P (2014),
https://hdl.handle.net/21.15107/rcub_vinar_9190 .

TY  - CONF
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Božović, N.
AU  - Đorđević, Jelena D.
AU  - Adžić, Miroslav
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9191
AB  - A growing body of evidence indicates extracellular signal-regulated kinase
(ERK1/2) participates in various stress-induced responses which isconsider
to beinvolved in pathophysiology of depression. Surprisingly, the effect of
antidepressants on ERKs is almost unexplored, particularly from the
perspective of sexes.In the present study, we investigated the potential role
of cytoplasm-nuclear distribution of phospho-ERK1/2 in the hippocampus
of chronically stressed female and male Wistar rats and if those potential
changes could be attenuated with chronic fluoxetine treatment. In females,
stress induced cytosolic retention of phospho-ERKs, while in
malesitpromoted the nuclear translocation of phospho-ERK 1/2. The effect
of concomitant fluoxetine treatment was more pronounced in stressed
females, with main focus on normalization of its nuclear phospho-ERK 1/2
levels.
PB  - Society of Physical Chemists of Serbia
C3  - Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry
T1  - Fluoxetine normalized nuclear phospho erk1/2 signaling in stressed females
VL  - F-11-P
UR  - https://hdl.handle.net/21.15107/rcub_vinar_9191
ER  - 

@conference{
author = "Mitić, Miloš and Lukić, Iva and Božović, N. and Đorđević, Jelena D. and Adžić, Miroslav",
year = "2014",
abstract = "A growing body of evidence indicates extracellular signal-regulated kinase
(ERK1/2) participates in various stress-induced responses which isconsider
to beinvolved in pathophysiology of depression. Surprisingly, the effect of
antidepressants on ERKs is almost unexplored, particularly from the
perspective of sexes.In the present study, we investigated the potential role
of cytoplasm-nuclear distribution of phospho-ERK1/2 in the hippocampus
of chronically stressed female and male Wistar rats and if those potential
changes could be attenuated with chronic fluoxetine treatment. In females,
stress induced cytosolic retention of phospho-ERKs, while in
malesitpromoted the nuclear translocation of phospho-ERK 1/2. The effect
of concomitant fluoxetine treatment was more pronounced in stressed
females, with main focus on normalization of its nuclear phospho-ERK 1/2
levels.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry",
title = "Fluoxetine normalized nuclear phospho erk1/2 signaling in stressed females",
volume = "F-11-P",
url = "https://hdl.handle.net/21.15107/rcub_vinar_9191"
}

Mitić, M., Lukić, I., Božović, N., Đorđević, J. D.,& Adžić, M.. (2014). Fluoxetine normalized nuclear phospho erk1/2 signaling in stressed females. in Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry
Society of Physical Chemists of Serbia., F-11-P.
https://hdl.handle.net/21.15107/rcub_vinar_9191

Mitić M, Lukić I, Božović N, Đorđević JD, Adžić M. Fluoxetine normalized nuclear phospho erk1/2 signaling in stressed females. in Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry. 2014;F-11-P.
https://hdl.handle.net/21.15107/rcub_vinar_9191 .

Mitić, Miloš, Lukić, Iva, Božović, N., Đorđević, Jelena D., Adžić, Miroslav, "Fluoxetine normalized nuclear phospho erk1/2 signaling in stressed females" in Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, F-11-P (2014),
https://hdl.handle.net/21.15107/rcub_vinar_9191 .

TY  - CONF
AU  - Brkić, Željka
AU  - Lukić, Iva
AU  - Mitić, Miloš
AU  - Božović, N.
AU  - Brašanac, Jelena
AU  - Đorđević, Jelena
AU  - Adžić, Miroslav
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9192
AB  - Systemic exposure to inflammatory challenges, such as lipopolysaccharide
(LPS), can induce a central neuroinflammation, which has been associated
with the development of major depressive disorder (MDD). Research data
emphasize not only sex as an important factor in the pathogenesis of MDD
but also point out a disturbance in cyclin-dependent kinase 5 (CDK5)
pathway. Therefore, in this study, we investigated the effects of LPS
treatment on depressive-like behavior as well as on the CDK5 and p35
levels in the cytosol and the nucleus of the prefrontal cortex of Wistar rats.
Our results showed that LPS causes a depressive-like behavior in both
sexes, as well as significant changes in the levels of CDK5 and p35, but
only in the males. Such differences of CDK5 activity could contribute to the
development of depressive-like behavior in males, while in females it seems
that some other mechanisms could be involved in the induction of this
behavior.
PB  - Society of Physical Chemists of Serbia
C3  - Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry
T1  - Involvement of prefrontal cortex cdk5 pathway in lps-induced depressive-like behavior in male and female wistar rats
VL  - F-12-P
UR  - https://hdl.handle.net/21.15107/rcub_vinar_9192
ER  - 

@conference{
author = "Brkić, Željka and Lukić, Iva and Mitić, Miloš and Božović, N. and Brašanac, Jelena and Đorđević, Jelena and Adžić, Miroslav",
year = "2014",
abstract = "Systemic exposure to inflammatory challenges, such as lipopolysaccharide
(LPS), can induce a central neuroinflammation, which has been associated
with the development of major depressive disorder (MDD). Research data
emphasize not only sex as an important factor in the pathogenesis of MDD
but also point out a disturbance in cyclin-dependent kinase 5 (CDK5)
pathway. Therefore, in this study, we investigated the effects of LPS
treatment on depressive-like behavior as well as on the CDK5 and p35
levels in the cytosol and the nucleus of the prefrontal cortex of Wistar rats.
Our results showed that LPS causes a depressive-like behavior in both
sexes, as well as significant changes in the levels of CDK5 and p35, but
only in the males. Such differences of CDK5 activity could contribute to the
development of depressive-like behavior in males, while in females it seems
that some other mechanisms could be involved in the induction of this
behavior.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry",
title = "Involvement of prefrontal cortex cdk5 pathway in lps-induced depressive-like behavior in male and female wistar rats",
volume = "F-12-P",
url = "https://hdl.handle.net/21.15107/rcub_vinar_9192"
}

Brkić, Ž., Lukić, I., Mitić, M., Božović, N., Brašanac, J., Đorđević, J.,& Adžić, M.. (2014). Involvement of prefrontal cortex cdk5 pathway in lps-induced depressive-like behavior in male and female wistar rats. in Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry
Society of Physical Chemists of Serbia., F-12-P.
https://hdl.handle.net/21.15107/rcub_vinar_9192

Brkić Ž, Lukić I, Mitić M, Božović N, Brašanac J, Đorđević J, Adžić M. Involvement of prefrontal cortex cdk5 pathway in lps-induced depressive-like behavior in male and female wistar rats. in Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry. 2014;F-12-P.
https://hdl.handle.net/21.15107/rcub_vinar_9192 .

Brkić, Željka, Lukić, Iva, Mitić, Miloš, Božović, N., Brašanac, Jelena, Đorđević, Jelena, Adžić, Miroslav, "Involvement of prefrontal cortex cdk5 pathway in lps-induced depressive-like behavior in male and female wistar rats" in Physical chemistry 2014: 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, F-12-P (2014),
https://hdl.handle.net/21.15107/rcub_vinar_9192 .