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  - Glavonić, Emilija
AU  - Mitić, Miloš
AU  - Francija, Ester
AU  - Petrović, Zorica
AU  - Adžić, Miroslav
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10514
AB  - Adolescence is a key phase of development for perturbations in fear extinction, with inability to adequately manage fear a potent factor for developing psychiatric disorders in adulthood. However, while behavioral correlates of adolescent fear regulation are established to a degree, molecular mediators of extinction learning in adolescence remain largely unknown. In this study, we observed fear acquisition and fear extinction (across 4 and 7 days) of adolescent and adult mice of both sexes and investigated how hippocampal levels of different plasticity markers relate to extinction learning. While fear was acquired evenly in males and females of both ages, fear extinction was found to be impaired in adolescent males. We also observed lower levels of GluA1, GLUN2A and GLUN2B subunits in male adolescents following fear acquisition, with an increase in their expression, as well as the activity of Erk-mTOR pathway over subsequent extinction sessions, which was paralleled with improved extinction learning. On the other hand, we detected no changes in plasticity-related proteins after fear acquisition in females, with alterations in GluA1, GluA4 and GLUN2B levels across fear extinction sessions. Additionally, we did not discern any pattern regarding the Erk-mTOR activity in female mice associated with their extinction performance. Overall, our research identifies sex-specific synaptic properties in the hippocampus that underlie developmentally regulated differences in fear extinction learning. We also point out hippocampal NMDA-Erk-mTOR signaling as the driving force behind successful fear extinction in male adolescents, highlighting this pathway as a potential therapeutic target for fear-related disorders in the adolescent population. © 2022 The Authors
T2  - Brain Research Bulletin
T1  - Sex-specific role of hippocampal NMDA-Erk-mTOR signaling in fear extinction of adolescent mice
VL  - 192
SP  - 156
EP  - 167
DO  - 10.1016/j.brainresbull.2022.11.011
ER  - 

@article{
author = "Glavonić, Emilija and Mitić, Miloš and Francija, Ester and Petrović, Zorica and Adžić, Miroslav",
year = "2023",
abstract = "Adolescence is a key phase of development for perturbations in fear extinction, with inability to adequately manage fear a potent factor for developing psychiatric disorders in adulthood. However, while behavioral correlates of adolescent fear regulation are established to a degree, molecular mediators of extinction learning in adolescence remain largely unknown. In this study, we observed fear acquisition and fear extinction (across 4 and 7 days) of adolescent and adult mice of both sexes and investigated how hippocampal levels of different plasticity markers relate to extinction learning. While fear was acquired evenly in males and females of both ages, fear extinction was found to be impaired in adolescent males. We also observed lower levels of GluA1, GLUN2A and GLUN2B subunits in male adolescents following fear acquisition, with an increase in their expression, as well as the activity of Erk-mTOR pathway over subsequent extinction sessions, which was paralleled with improved extinction learning. On the other hand, we detected no changes in plasticity-related proteins after fear acquisition in females, with alterations in GluA1, GluA4 and GLUN2B levels across fear extinction sessions. Additionally, we did not discern any pattern regarding the Erk-mTOR activity in female mice associated with their extinction performance. Overall, our research identifies sex-specific synaptic properties in the hippocampus that underlie developmentally regulated differences in fear extinction learning. We also point out hippocampal NMDA-Erk-mTOR signaling as the driving force behind successful fear extinction in male adolescents, highlighting this pathway as a potential therapeutic target for fear-related disorders in the adolescent population. © 2022 The Authors",
journal = "Brain Research Bulletin",
title = "Sex-specific role of hippocampal NMDA-Erk-mTOR signaling in fear extinction of adolescent mice",
volume = "192",
pages = "156-167",
doi = "10.1016/j.brainresbull.2022.11.011"
}

Glavonić, E., Mitić, M., Francija, E., Petrović, Z.,& Adžić, M.. (2023). Sex-specific role of hippocampal NMDA-Erk-mTOR signaling in fear extinction of adolescent mice. in Brain Research Bulletin, 192, 156-167.
https://doi.org/10.1016/j.brainresbull.2022.11.011

Glavonić E, Mitić M, Francija E, Petrović Z, Adžić M. Sex-specific role of hippocampal NMDA-Erk-mTOR signaling in fear extinction of adolescent mice. in Brain Research Bulletin. 2023;192:156-167.
doi:10.1016/j.brainresbull.2022.11.011 .

Glavonić, Emilija, Mitić, Miloš, Francija, Ester, Petrović, Zorica, Adžić, Miroslav, "Sex-specific role of hippocampal NMDA-Erk-mTOR signaling in fear extinction of adolescent mice" in Brain Research Bulletin, 192 (2023):156-167,
https://doi.org/10.1016/j.brainresbull.2022.11.011 . .

TY  - JOUR
AU  - Glavonić, Emilija
AU  - Mitić, Miloš
AU  - Adžić, Miroslav
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10165
AB  - Fear-related disorders, mainly phobias and post-traumatic stress disorder, are highly prevalent, debilitating disorders that pose a significant public health problem. They are characterized by aberrant processing of aversive experiences and dysregulated fear extinction, leading to excessive expression of fear and diminished quality of life. The gold standard for treating fear-related disorders is extinction-based exposure therapy (ET), shown to be ineffective for up to 35% of subjects. Moreover, ET combined with traditional pharmacological treatments for fear-related disorders, such as selective serotonin reuptake inhibitors, offers no further advantage to patients. This prompted the search for ways to improve ET outcomes, with current research focused on pharmacological agents that can augment ET by strengthening fear extinction learning. Hallucinogenic drugs promote reprocessing of fear-imbued memories and induce positive mood and openness, relieving anxiety and enabling the necessary emotional engagement during psychotherapeutic interventions. Mechanistically, hallucinogens induce dynamic structural and functional neuroplastic changes across the fear extinction circuitry and temper amygdala's hyperreactivity to threat-related stimuli, effectively mitigating one of the hallmarks of fear-related disorders. This paper provides the first comprehensive review of hallucinogens' potential to alleviate symptoms of fear-related disorders by focusing on their effects on fear extinction and the underlying molecular mechanisms. We overview both preclinical and clinical studies and emphasize the advantages of hallucinogenic drugs over current first-line treatments. We highlight 3,4-methylenedioxymethamphetamine and ketamine as the most effective therapeutics for fear-related disorders and discuss the potential molecular mechanisms responsible for their potency with implications for improving hallucinogen-assisted psychotherapy.
T2  - Journal of Neuroscience Research
T1  - Hallucinogenic drugs and their potential for treating fear-related disorders: Through the lens of fear extinction
VL  - 100
IS  - 4
SP  - 947
EP  - 969
DO  - 10.1002/jnr.25017
ER  - 

@article{
author = "Glavonić, Emilija and Mitić, Miloš and Adžić, Miroslav",
year = "2022",
abstract = "Fear-related disorders, mainly phobias and post-traumatic stress disorder, are highly prevalent, debilitating disorders that pose a significant public health problem. They are characterized by aberrant processing of aversive experiences and dysregulated fear extinction, leading to excessive expression of fear and diminished quality of life. The gold standard for treating fear-related disorders is extinction-based exposure therapy (ET), shown to be ineffective for up to 35% of subjects. Moreover, ET combined with traditional pharmacological treatments for fear-related disorders, such as selective serotonin reuptake inhibitors, offers no further advantage to patients. This prompted the search for ways to improve ET outcomes, with current research focused on pharmacological agents that can augment ET by strengthening fear extinction learning. Hallucinogenic drugs promote reprocessing of fear-imbued memories and induce positive mood and openness, relieving anxiety and enabling the necessary emotional engagement during psychotherapeutic interventions. Mechanistically, hallucinogens induce dynamic structural and functional neuroplastic changes across the fear extinction circuitry and temper amygdala's hyperreactivity to threat-related stimuli, effectively mitigating one of the hallmarks of fear-related disorders. This paper provides the first comprehensive review of hallucinogens' potential to alleviate symptoms of fear-related disorders by focusing on their effects on fear extinction and the underlying molecular mechanisms. We overview both preclinical and clinical studies and emphasize the advantages of hallucinogenic drugs over current first-line treatments. We highlight 3,4-methylenedioxymethamphetamine and ketamine as the most effective therapeutics for fear-related disorders and discuss the potential molecular mechanisms responsible for their potency with implications for improving hallucinogen-assisted psychotherapy.",
journal = "Journal of Neuroscience Research",
title = "Hallucinogenic drugs and their potential for treating fear-related disorders: Through the lens of fear extinction",
volume = "100",
number = "4",
pages = "947-969",
doi = "10.1002/jnr.25017"
}

Glavonić, E., Mitić, M.,& Adžić, M.. (2022). Hallucinogenic drugs and their potential for treating fear-related disorders: Through the lens of fear extinction. in Journal of Neuroscience Research, 100(4), 947-969.
https://doi.org/10.1002/jnr.25017

Glavonić E, Mitić M, Adžić M. Hallucinogenic drugs and their potential for treating fear-related disorders: Through the lens of fear extinction. in Journal of Neuroscience Research. 2022;100(4):947-969.
doi:10.1002/jnr.25017 .

Glavonić, Emilija, Mitić, Miloš, Adžić, Miroslav, "Hallucinogenic drugs and their potential for treating fear-related disorders: Through the lens of fear extinction" in Journal of Neuroscience Research, 100, no. 4 (2022):947-969,
https://doi.org/10.1002/jnr.25017 . .

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  - Ivković, Sanja
AU  - Major, Tamara
AU  - Mitić, Miloš
AU  - Lončarević-Vasiljković, Nataša
AU  - Jović, Milena
AU  - Adžić, Miroslav
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10220
AB  - The brain is the softest organ in the body, and any change in the mechanical properties of the tissue induces the activation of glial cells, astrocytes and microglia. Amyloid plaques, one of the main pathological features of Alzheimer's disease (AD), are substantially harder than the surrounding brain tissue and can activate astrocytes and microglia resulting in the glial engulfment of plaques. Durotaxis, a migratory preference towards stiffer tissue, is prompting microglia to form a mechanical barrier around plaques reducing amyloid β (Aβ) induced neurotoxicity. Mechanoreceptors are highly expressed in the brain, particularly in microglia. The large increase in the expression of the mechanoreceptor Piezo1 was observed in the brains from AD animal models and AD patients in plaque encompassing glia. Importantly, Piezo1 function is regulated via force-from–lipids through the lipid composition of the membrane and membranous incorporation of polyunsaturated fatty acids (PUFAs) can affect the function of Piezo1 altering mechanosensitive properties of the cell. On the other hand, PUFAs dietary supplementation can alter microglial polarization, the envelopment of amyloid plaques, and immune response and Piezo1 activity was implicated in the similar modulations of microglia behavior. Finally, PUFAs treatment is currently in use in medical trials as the therapy for sickle cell anemia, a disease linked with the mutations in Piezo1. Further studies are needed to elucidate the connection between PUFAs, Piezo1 expression, and microglia behavior in the AD brain. These findings could open new possibilities in harnessing microglia in AD and in developing novel therapeutic strategies.
T2  - Life Sciences
T1  - Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease
VL  - 297
DO  - 10.1016/j.lfs.2022.120470
ER  - 

@article{
author = "Ivković, Sanja and Major, Tamara and Mitić, Miloš and Lončarević-Vasiljković, Nataša and Jović, Milena and Adžić, Miroslav",
year = "2022",
abstract = "The brain is the softest organ in the body, and any change in the mechanical properties of the tissue induces the activation of glial cells, astrocytes and microglia. Amyloid plaques, one of the main pathological features of Alzheimer's disease (AD), are substantially harder than the surrounding brain tissue and can activate astrocytes and microglia resulting in the glial engulfment of plaques. Durotaxis, a migratory preference towards stiffer tissue, is prompting microglia to form a mechanical barrier around plaques reducing amyloid β (Aβ) induced neurotoxicity. Mechanoreceptors are highly expressed in the brain, particularly in microglia. The large increase in the expression of the mechanoreceptor Piezo1 was observed in the brains from AD animal models and AD patients in plaque encompassing glia. Importantly, Piezo1 function is regulated via force-from–lipids through the lipid composition of the membrane and membranous incorporation of polyunsaturated fatty acids (PUFAs) can affect the function of Piezo1 altering mechanosensitive properties of the cell. On the other hand, PUFAs dietary supplementation can alter microglial polarization, the envelopment of amyloid plaques, and immune response and Piezo1 activity was implicated in the similar modulations of microglia behavior. Finally, PUFAs treatment is currently in use in medical trials as the therapy for sickle cell anemia, a disease linked with the mutations in Piezo1. Further studies are needed to elucidate the connection between PUFAs, Piezo1 expression, and microglia behavior in the AD brain. These findings could open new possibilities in harnessing microglia in AD and in developing novel therapeutic strategies.",
journal = "Life Sciences",
title = "Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease",
volume = "297",
doi = "10.1016/j.lfs.2022.120470"
}

Ivković, S., Major, T., Mitić, M., Lončarević-Vasiljković, N., Jović, M.,& Adžić, M.. (2022). Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease. in Life Sciences, 297.
https://doi.org/10.1016/j.lfs.2022.120470

Ivković S, Major T, Mitić M, Lončarević-Vasiljković N, Jović M, Adžić M. Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease. in Life Sciences. 2022;297.
doi:10.1016/j.lfs.2022.120470 .

Ivković, Sanja, Major, Tamara, Mitić, Miloš, Lončarević-Vasiljković, Nataša, Jović, Milena, Adžić, Miroslav, "Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease" in Life Sciences, 297 (2022),
https://doi.org/10.1016/j.lfs.2022.120470 . .

TY  - JOUR
AU  - Dubljević, Olga
AU  - Ković, Vanja
AU  - Pavković, Željko
AU  - Mitić, Miloš
AU  - Pešić, Vesna
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10482
AB  - A potential relationship between unrestricted sucrose intake (USI), overweight, and emotional/behavioral control has not been well documented. We examined the influence of USI and having less sweetness than expected on body weight (BW), motor/exploratory, anxiety-like, and social dominant behavior in adult C57BL/6J male mice. Animals had free access to water (group 1) or 32% sucrose and water (sucrose groups 2–5) for 10 days. Then, group 2 remained with 32% sucrose while groups 3–5 were subjected to the downshift (24 h access to 4%, 8%, or 16% sucrose). All experimental groups were weighed and tested in the novel-open arena (NA), elevated plus maze (EPM), and tube tests to assess BW, motor/exploratory, anxiety-like, and social dominance behavior, respectively. USI did not influence animals’ BW but produced hyperactivity and anxiolytic-like behavior, which was evident in EPM but not in NA; the outcomes of the downshift were comparable. USI did not influence successes/wins in the tube test but altered emotions that drive the winning, favoring a less anxious behavioral phenotype; this was not evident in the downshifted groups. Observed findings suggest that USI promotes sensation-seeking and motivates dominance, without changing BW, while blunted emotional base of social dominance might be an early mark of the downshift.
T2  - Brain Sciences
T1  - The Influence of Unlimited Sucrose Intake on Body Weight and Behavior—Findings from a Mouse Model
VL  - 12
IS  - 10
SP  - 1332
DO  - 10.3390/brainsci12101332
ER  - 

@article{
author = "Dubljević, Olga and Ković, Vanja and Pavković, Željko and Mitić, Miloš and Pešić, Vesna",
year = "2022",
abstract = "A potential relationship between unrestricted sucrose intake (USI), overweight, and emotional/behavioral control has not been well documented. We examined the influence of USI and having less sweetness than expected on body weight (BW), motor/exploratory, anxiety-like, and social dominant behavior in adult C57BL/6J male mice. Animals had free access to water (group 1) or 32% sucrose and water (sucrose groups 2–5) for 10 days. Then, group 2 remained with 32% sucrose while groups 3–5 were subjected to the downshift (24 h access to 4%, 8%, or 16% sucrose). All experimental groups were weighed and tested in the novel-open arena (NA), elevated plus maze (EPM), and tube tests to assess BW, motor/exploratory, anxiety-like, and social dominance behavior, respectively. USI did not influence animals’ BW but produced hyperactivity and anxiolytic-like behavior, which was evident in EPM but not in NA; the outcomes of the downshift were comparable. USI did not influence successes/wins in the tube test but altered emotions that drive the winning, favoring a less anxious behavioral phenotype; this was not evident in the downshifted groups. Observed findings suggest that USI promotes sensation-seeking and motivates dominance, without changing BW, while blunted emotional base of social dominance might be an early mark of the downshift.",
journal = "Brain Sciences",
title = "The Influence of Unlimited Sucrose Intake on Body Weight and Behavior—Findings from a Mouse Model",
volume = "12",
number = "10",
pages = "1332",
doi = "10.3390/brainsci12101332"
}

Dubljević, O., Ković, V., Pavković, Ž., Mitić, M.,& Pešić, V.. (2022). The Influence of Unlimited Sucrose Intake on Body Weight and Behavior—Findings from a Mouse Model. in Brain Sciences, 12(10), 1332.
https://doi.org/10.3390/brainsci12101332

Dubljević O, Ković V, Pavković Ž, Mitić M, Pešić V. The Influence of Unlimited Sucrose Intake on Body Weight and Behavior—Findings from a Mouse Model. in Brain Sciences. 2022;12(10):1332.
doi:10.3390/brainsci12101332 .

Dubljević, Olga, Ković, Vanja, Pavković, Željko, Mitić, Miloš, Pešić, Vesna, "The Influence of Unlimited Sucrose Intake on Body Weight and Behavior—Findings from a Mouse Model" in Brain Sciences, 12, no. 10 (2022):1332,
https://doi.org/10.3390/brainsci12101332 . .

TY  - JOUR
AU  - Mitić, Miloš
AU  - Lazarević-Pašti, Tamara
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9839
AB  - Alzheimer’s disease and depression are health conditions affecting millions of people around the world. Both are strongly related to the level of the neurotransmitter acetylcholine. Since cholinergic deficit is characteristic of Alzheimer’s disease, acetylcholinesterase inhibitors are applied as relevant drugs for the treatment of this disease, elevating the level of acetylcholine. On the other hand, a high level of acetylcholine is found to be associated with the symptoms of clinical depression. Areas covered: This article aims to discuss if acetylcholinesterase inhibitors used as anti-Alzheimer’s drugs could be the cause of the symptoms of clinical depression often linked to this neurological disorder. Emphasis will be put on drugs currently in use and on newly investigated natural products, which can inhibit AChE activity. Expert opinion: Currently, it is not proven that the patient treated for Alzheimer’s disease is prone to increased risk for depression due to the acetylcholinesterase inhibition, but there are strong indications. The level of acetylcholine is not the only factor in highly complicated diseases like AD and depression. Still, it needs to be considered isolated, keeping in mind the nature of presently available therapy, especially during a rational drug design process. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
T2  - Expert Opinion on Drug Metabolism and Toxicology
T1  - Does the application of acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease lead to depression?
VL  - 17
IS  - 7
SP  - 841
EP  - 856
DO  - 10.1080/17425255.2021.1931681
ER  - 

@article{
author = "Mitić, Miloš and Lazarević-Pašti, Tamara",
year = "2021",
abstract = "Alzheimer’s disease and depression are health conditions affecting millions of people around the world. Both are strongly related to the level of the neurotransmitter acetylcholine. Since cholinergic deficit is characteristic of Alzheimer’s disease, acetylcholinesterase inhibitors are applied as relevant drugs for the treatment of this disease, elevating the level of acetylcholine. On the other hand, a high level of acetylcholine is found to be associated with the symptoms of clinical depression. Areas covered: This article aims to discuss if acetylcholinesterase inhibitors used as anti-Alzheimer’s drugs could be the cause of the symptoms of clinical depression often linked to this neurological disorder. Emphasis will be put on drugs currently in use and on newly investigated natural products, which can inhibit AChE activity. Expert opinion: Currently, it is not proven that the patient treated for Alzheimer’s disease is prone to increased risk for depression due to the acetylcholinesterase inhibition, but there are strong indications. The level of acetylcholine is not the only factor in highly complicated diseases like AD and depression. Still, it needs to be considered isolated, keeping in mind the nature of presently available therapy, especially during a rational drug design process. © 2021 Informa UK Limited, trading as Taylor & Francis Group.",
journal = "Expert Opinion on Drug Metabolism and Toxicology",
title = "Does the application of acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease lead to depression?",
volume = "17",
number = "7",
pages = "841-856",
doi = "10.1080/17425255.2021.1931681"
}

Mitić, M.,& Lazarević-Pašti, T.. (2021). Does the application of acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease lead to depression?. in Expert Opinion on Drug Metabolism and Toxicology, 17(7), 841-856.
https://doi.org/10.1080/17425255.2021.1931681

Mitić M, Lazarević-Pašti T. Does the application of acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease lead to depression?. in Expert Opinion on Drug Metabolism and Toxicology. 2021;17(7):841-856.
doi:10.1080/17425255.2021.1931681 .

Mitić, Miloš, Lazarević-Pašti, Tamara, "Does the application of acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease lead to depression?" in Expert Opinion on Drug Metabolism and Toxicology, 17, no. 7 (2021):841-856,
https://doi.org/10.1080/17425255.2021.1931681 . .

TY  - JOUR
AU  - Radić, Ivan
AU  - Mirić, Mirjana
AU  - Mijović, Milica
AU  - Tatalović, Nikola
AU  - Mitić, Miloš
AU  - Nestorović, Vojkan
AU  - Adžić, Miroslav
AU  - Blagojević, Duško
AU  - Popović, Ljiljana
AU  - Janićijević-Hudomal, Snežana
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9412
AB  - Pumpkin seed oil (PSO) possesses a protective potential against liver injury due to the presence of biologically active ingredients. Adult male albino rats were administrated PSO (per os, 2 mL/kg b.w./day) and a 12% ethanol solution in water, ad libitum, with an average intake of 8.14 g of ethanol/kg bw/day for 6 weeks. Congestion, hepatic central vein dilation, portal vein branch dilation, Kupffer cell hyperplasia, fatty liver changes, hepatocyte focal necrosis were observed after daily alcohol intake. All observed changes were reduced when PSO was ingested with ethanol. PSO intake itself induced discrete cellular edema, congestion and slight dilatation of the central and portal vain branches. Chronic ethanol intake elevated catalase (CAT) activity and glutathione reductase (GR) protein expression; concomitant PSO intake had no effect on CAT activity or GR protein expression. PSO intake decreased the activities of GR, glutathione-S-transferase (GST) and xanthine oxidase (XOD) in the liver, probably due to the ingestion of antioxidants. Intake of PSO and ethanol significantly decreased cytosolic superoxide dismutase (SOD1) and increased NF-?B protein expression compared to ethanol intake, suggesting that the protective effects of PSO were mediated by the NF-?B signaling pathway. Our results reveal a therapeutic potential of PSO in alcoholic liver disease.
T2  - Archives of Biological Sciences
T1  - Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption
VL  - 73
IS  - 1
SP  - 123
EP  - 133
DO  - 10.2298/ABS201205008R
ER  - 

@article{
author = "Radić, Ivan and Mirić, Mirjana and Mijović, Milica and Tatalović, Nikola and Mitić, Miloš and Nestorović, Vojkan and Adžić, Miroslav and Blagojević, Duško and Popović, Ljiljana and Janićijević-Hudomal, Snežana",
year = "2021",
abstract = "Pumpkin seed oil (PSO) possesses a protective potential against liver injury due to the presence of biologically active ingredients. Adult male albino rats were administrated PSO (per os, 2 mL/kg b.w./day) and a 12% ethanol solution in water, ad libitum, with an average intake of 8.14 g of ethanol/kg bw/day for 6 weeks. Congestion, hepatic central vein dilation, portal vein branch dilation, Kupffer cell hyperplasia, fatty liver changes, hepatocyte focal necrosis were observed after daily alcohol intake. All observed changes were reduced when PSO was ingested with ethanol. PSO intake itself induced discrete cellular edema, congestion and slight dilatation of the central and portal vain branches. Chronic ethanol intake elevated catalase (CAT) activity and glutathione reductase (GR) protein expression; concomitant PSO intake had no effect on CAT activity or GR protein expression. PSO intake decreased the activities of GR, glutathione-S-transferase (GST) and xanthine oxidase (XOD) in the liver, probably due to the ingestion of antioxidants. Intake of PSO and ethanol significantly decreased cytosolic superoxide dismutase (SOD1) and increased NF-?B protein expression compared to ethanol intake, suggesting that the protective effects of PSO were mediated by the NF-?B signaling pathway. Our results reveal a therapeutic potential of PSO in alcoholic liver disease.",
journal = "Archives of Biological Sciences",
title = "Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption",
volume = "73",
number = "1",
pages = "123-133",
doi = "10.2298/ABS201205008R"
}

Radić, I., Mirić, M., Mijović, M., Tatalović, N., Mitić, M., Nestorović, V., Adžić, M., Blagojević, D., Popović, L.,& Janićijević-Hudomal, S.. (2021). Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption. in Archives of Biological Sciences, 73(1), 123-133.
https://doi.org/10.2298/ABS201205008R

Radić I, Mirić M, Mijović M, Tatalović N, Mitić M, Nestorović V, Adžić M, Blagojević D, Popović L, Janićijević-Hudomal S. Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption. in Archives of Biological Sciences. 2021;73(1):123-133.
doi:10.2298/ABS201205008R .

Radić, Ivan, Mirić, Mirjana, Mijović, Milica, Tatalović, Nikola, Mitić, Miloš, Nestorović, Vojkan, Adžić, Miroslav, Blagojević, Duško, Popović, Ljiljana, Janićijević-Hudomal, Snežana, "Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption" in Archives of Biological Sciences, 73, no. 1 (2021):123-133,
https://doi.org/10.2298/ABS201205008R . .

TY  - JOUR
AU  - Francija, Ester
AU  - Petrović, Zorica
AU  - Brkić, Željka
AU  - Mitić, Miloš
AU  - Radulović, Jelena
AU  - Adžić, Miroslav
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8450
AB  - Recent reports have demonstrated that lipopolysaccharide (LPS)-induced depressive-like behaviour is mediated via NMDA receptor. In this study, we further investigated the role of GluN2 A subunit of NMDA receptor in synaptic processes in the prefrontal cortex (PFC) and hippocampus of GluN2 A knockout (KO) mice in LPS-induced depressive-like behavior. Our data suggest that LPS-treated mice, lacking GluN2 A subunit, did not exhibit depressive-like behaviour. This was accompanied by unaltered levels of IL-6 and significant changes in neuroplasticity markers and glutamate receptor subunits composition in PFC and hippocampus. In particular, an immune challenge in GluN2 A KO mice resulted in unchanged PSA-NCAM levels and proBDNF increase in both brain structures as well as in increase in BDNF levels in hippocampus. Furthermore, the absence of GluN2 A resulted in increased levels of all NCAM isoforms in PFC upon LPS which was followed with a decrease in GluN1 and GluN2B subunits. The levels of AMPA receptor subunits (GluA1, GluA3, and GluA4) in the hippocampus of GluN2 A mice were unaltered upon the treatment and abundantly present in the PFC of KO mice. These results indicate that the GluN2 A subunit is critical in neuroinflammation-related depression, that its absence abolishes LPS-induced depressive phenotype, sustains PSA-NCAM levels, increases proBDNF signalling in the PFC and hippocampus and potentiates synaptic stabilization through NCAM in the PFC upon an immune challenge. © 2018 Elsevier B.V.
T2  - Behavioural Brain Research
T1  - Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression
VL  - 359
SP  - 550
EP  - 559
DO  - 10.1016/j.bbr.2018.10.011
ER  - 

@article{
author = "Francija, Ester and Petrović, Zorica and Brkić, Željka and Mitić, Miloš and Radulović, Jelena and Adžić, Miroslav",
year = "2019",
abstract = "Recent reports have demonstrated that lipopolysaccharide (LPS)-induced depressive-like behaviour is mediated via NMDA receptor. In this study, we further investigated the role of GluN2 A subunit of NMDA receptor in synaptic processes in the prefrontal cortex (PFC) and hippocampus of GluN2 A knockout (KO) mice in LPS-induced depressive-like behavior. Our data suggest that LPS-treated mice, lacking GluN2 A subunit, did not exhibit depressive-like behaviour. This was accompanied by unaltered levels of IL-6 and significant changes in neuroplasticity markers and glutamate receptor subunits composition in PFC and hippocampus. In particular, an immune challenge in GluN2 A KO mice resulted in unchanged PSA-NCAM levels and proBDNF increase in both brain structures as well as in increase in BDNF levels in hippocampus. Furthermore, the absence of GluN2 A resulted in increased levels of all NCAM isoforms in PFC upon LPS which was followed with a decrease in GluN1 and GluN2B subunits. The levels of AMPA receptor subunits (GluA1, GluA3, and GluA4) in the hippocampus of GluN2 A mice were unaltered upon the treatment and abundantly present in the PFC of KO mice. These results indicate that the GluN2 A subunit is critical in neuroinflammation-related depression, that its absence abolishes LPS-induced depressive phenotype, sustains PSA-NCAM levels, increases proBDNF signalling in the PFC and hippocampus and potentiates synaptic stabilization through NCAM in the PFC upon an immune challenge. © 2018 Elsevier B.V.",
journal = "Behavioural Brain Research",
title = "Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression",
volume = "359",
pages = "550-559",
doi = "10.1016/j.bbr.2018.10.011"
}

Francija, E., Petrović, Z., Brkić, Ž., Mitić, M., Radulović, J.,& Adžić, M.. (2019). Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression. in Behavioural Brain Research, 359, 550-559.
https://doi.org/10.1016/j.bbr.2018.10.011

Francija E, Petrović Z, Brkić Ž, Mitić M, Radulović J, Adžić M. Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression. in Behavioural Brain Research. 2019;359:550-559.
doi:10.1016/j.bbr.2018.10.011 .

Francija, Ester, Petrović, Zorica, Brkić, Željka, Mitić, Miloš, Radulović, Jelena, Adžić, Miroslav, "Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression" in Behavioural Brain Research, 359 (2019):550-559,
https://doi.org/10.1016/j.bbr.2018.10.011 . .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Glavonić, Emilija
AU  - Nešić, Milica J.
AU  - Milosavljević, Minja
AU  - Mihaljević, Marina
AU  - Petrović, Zorica D.
AU  - Pavlović, Zorana
AU  - Brkić, Željka
AU  - Francija, Ester
AU  - Soldatović, Ivan A.
AU  - Mitić, Miloš
AU  - Radulović, Jelena
AU  - Marić, Nađa P.
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8010
AB  - Childhood trauma (CT) increases the risk for psychopathology through disturbed acquisition and extinction of fear. The effects of CT are mediated by abnormalities of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor (GR). Since, the alterations in GRα translational isoforms have been documented in psychiatric disorders we sought to: 1) explore whether multiple GRα isoforms in the human peripheral blood mononuclear cells of two independent cohorts (whole cell n = 40; and nuclear extracts n = 43, adult subjects) mediate the effect of CT on negative affectivity (NA) measured by Depression, Anxiety and Stress Scales (DASS), and 2) examine their role/function during fear extinction in the animal model. In multiple regression analysis, CT, nuclear 40-kDa GRα their interactions and FKBP5 explained 22%–35% of variance in DASS scores. Structural equation modeling showed that CT had a significant direct effect on 40-kDa and DASS in both cohorts, and on the nuclear 25-kDa GRα. The association between 40-kDa and total DASS was significantly mediated by nuclear FKBP5, whereas on DASS anxiety, over FKBP5 in both cohorts and nuclear full length GRα. Nuclear 40-kDa GRα and its interaction with CT had a significant direct effect on DASS anxiety. In mice, the successful extinction learning was followed by nuclear translocation of 40-kDa GRα and induction of BDNF exon IV expression. Our data revealed that the association between CT and adult NA in non-clinical subjects is mediated by the GRα translational isoforms, in particular 40-kDa GRα and emphasized its role in fear extinction and neural plasticity. © 2018 Elsevier Inc.
T2  - Progress in Neuro-Psychopharmacology and Biological Psychiatry
T1  - Glucocorticoid receptor alpha translational isoforms as mediators of early adversities and negative emotional states
VL  - 90
SP  - 288
EP  - 299
DO  - 10.1016/j.pnpbp.2018.12.011
ER  - 

@article{
author = "Adžić, Miroslav and Glavonić, Emilija and Nešić, Milica J. and Milosavljević, Minja and Mihaljević, Marina and Petrović, Zorica D. and Pavlović, Zorana and Brkić, Željka and Francija, Ester and Soldatović, Ivan A. and Mitić, Miloš and Radulović, Jelena and Marić, Nađa P.",
year = "2019",
abstract = "Childhood trauma (CT) increases the risk for psychopathology through disturbed acquisition and extinction of fear. The effects of CT are mediated by abnormalities of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor (GR). Since, the alterations in GRα translational isoforms have been documented in psychiatric disorders we sought to: 1) explore whether multiple GRα isoforms in the human peripheral blood mononuclear cells of two independent cohorts (whole cell n = 40; and nuclear extracts n = 43, adult subjects) mediate the effect of CT on negative affectivity (NA) measured by Depression, Anxiety and Stress Scales (DASS), and 2) examine their role/function during fear extinction in the animal model. In multiple regression analysis, CT, nuclear 40-kDa GRα their interactions and FKBP5 explained 22%–35% of variance in DASS scores. Structural equation modeling showed that CT had a significant direct effect on 40-kDa and DASS in both cohorts, and on the nuclear 25-kDa GRα. The association between 40-kDa and total DASS was significantly mediated by nuclear FKBP5, whereas on DASS anxiety, over FKBP5 in both cohorts and nuclear full length GRα. Nuclear 40-kDa GRα and its interaction with CT had a significant direct effect on DASS anxiety. In mice, the successful extinction learning was followed by nuclear translocation of 40-kDa GRα and induction of BDNF exon IV expression. Our data revealed that the association between CT and adult NA in non-clinical subjects is mediated by the GRα translational isoforms, in particular 40-kDa GRα and emphasized its role in fear extinction and neural plasticity. © 2018 Elsevier Inc.",
journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",
title = "Glucocorticoid receptor alpha translational isoforms as mediators of early adversities and negative emotional states",
volume = "90",
pages = "288-299",
doi = "10.1016/j.pnpbp.2018.12.011"
}

Adžić, M., Glavonić, E., Nešić, M. J., Milosavljević, M., Mihaljević, M., Petrović, Z. D., Pavlović, Z., Brkić, Ž., Francija, E., Soldatović, I. A., Mitić, M., Radulović, J.,& Marić, N. P.. (2019). Glucocorticoid receptor alpha translational isoforms as mediators of early adversities and negative emotional states. in Progress in Neuro-Psychopharmacology and Biological Psychiatry, 90, 288-299.
https://doi.org/10.1016/j.pnpbp.2018.12.011

Adžić M, Glavonić E, Nešić MJ, Milosavljević M, Mihaljević M, Petrović ZD, Pavlović Z, Brkić Ž, Francija E, Soldatović IA, Mitić M, Radulović J, Marić NP. Glucocorticoid receptor alpha translational isoforms as mediators of early adversities and negative emotional states. in Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2019;90:288-299.
doi:10.1016/j.pnpbp.2018.12.011 .

Adžić, Miroslav, Glavonić, Emilija, Nešić, Milica J., Milosavljević, Minja, Mihaljević, Marina, Petrović, Zorica D., Pavlović, Zorana, Brkić, Željka, Francija, Ester, Soldatović, Ivan A., Mitić, Miloš, Radulović, Jelena, Marić, Nađa P., "Glucocorticoid receptor alpha translational isoforms as mediators of early adversities and negative emotional states" in Progress in Neuro-Psychopharmacology and Biological Psychiatry, 90 (2019):288-299,
https://doi.org/10.1016/j.pnpbp.2018.12.011 . .

TY  - JOUR
AU  - Radić, Ivan
AU  - Mijović, Milica
AU  - Tatalović, Nikola R.
AU  - Mitić, Miloš
AU  - Lukić, Vera
AU  - Joksimović, Bojan
AU  - Petrović, Zorica
AU  - Ristić, Siniša
AU  - Veličković, Stefan
AU  - Nestorović, Vojkan
AU  - Ćorac, Aleksandar M.
AU  - Mirić, Mirjana
AU  - Adžić, Miroslav
AU  - Blagojević, Duško P.
AU  - Popović, Ljiljana M.
AU  - Janićijević-Hudomal, Snežana
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8541
AB  - In 2012, alcohol liver disease resulted in 3.3 million—5.9% of global deaths. This study introduced whey protection capacity against chronic alcohol-induced liver injury. Rats were orally administered to 12% ethanol solution in water (ad libitum, average 8.14 g of ethanol/kg body weight (b.w.)/day) alone or combined with whey (per os, 2 g/kg b.w./day). After 6-week treatment, chronic ethanol consumption induced significant histopathological liver changes: congestion, central vein dilation, hepatic portal vein branch dilation, Kupffer cells hyperplasia, fatty liver changes, and hepatocytes focal necrosis. Ethanol significantly increased liver catalase activity and glutathione reductase protein expression without significant effects on antioxidative enzymes: glutathione peroxidase (GPx), copper–zinc-containing superoxide dismutase (CuZnSOD) and manganese-containing superoxide dismutase (MnSOD). Co-treatment with whey significantly attenuated pathohistological changes induced by ethanol ingestion and increased GSH-Px and nuclear factor kappa B (NF-κB) protein expression. Our results showed positive effects of whey on liver chronically exposed to ethanol, which seem to be associated with NF-κB-GPx signaling. © The Author(s) 2019.
T2  - Human and Experimental Toxicology
T1  - Protective effects of whey on rat liver damage induced by chronic alcohol intake
VL  - 38
IS  - 6
SP  - 632
EP  - 645
DO  - 10.1177/0960327119829518
ER  - 

@article{
author = "Radić, Ivan and Mijović, Milica and Tatalović, Nikola R. and Mitić, Miloš and Lukić, Vera and Joksimović, Bojan and Petrović, Zorica and Ristić, Siniša and Veličković, Stefan and Nestorović, Vojkan and Ćorac, Aleksandar M. and Mirić, Mirjana and Adžić, Miroslav and Blagojević, Duško P. and Popović, Ljiljana M. and Janićijević-Hudomal, Snežana",
year = "2019",
abstract = "In 2012, alcohol liver disease resulted in 3.3 million—5.9% of global deaths. This study introduced whey protection capacity against chronic alcohol-induced liver injury. Rats were orally administered to 12% ethanol solution in water (ad libitum, average 8.14 g of ethanol/kg body weight (b.w.)/day) alone or combined with whey (per os, 2 g/kg b.w./day). After 6-week treatment, chronic ethanol consumption induced significant histopathological liver changes: congestion, central vein dilation, hepatic portal vein branch dilation, Kupffer cells hyperplasia, fatty liver changes, and hepatocytes focal necrosis. Ethanol significantly increased liver catalase activity and glutathione reductase protein expression without significant effects on antioxidative enzymes: glutathione peroxidase (GPx), copper–zinc-containing superoxide dismutase (CuZnSOD) and manganese-containing superoxide dismutase (MnSOD). Co-treatment with whey significantly attenuated pathohistological changes induced by ethanol ingestion and increased GSH-Px and nuclear factor kappa B (NF-κB) protein expression. Our results showed positive effects of whey on liver chronically exposed to ethanol, which seem to be associated with NF-κB-GPx signaling. © The Author(s) 2019.",
journal = "Human and Experimental Toxicology",
title = "Protective effects of whey on rat liver damage induced by chronic alcohol intake",
volume = "38",
number = "6",
pages = "632-645",
doi = "10.1177/0960327119829518"
}

Radić, I., Mijović, M., Tatalović, N. R., Mitić, M., Lukić, V., Joksimović, B., Petrović, Z., Ristić, S., Veličković, S., Nestorović, V., Ćorac, A. M., Mirić, M., Adžić, M., Blagojević, D. P., Popović, L. M.,& Janićijević-Hudomal, S.. (2019). Protective effects of whey on rat liver damage induced by chronic alcohol intake. in Human and Experimental Toxicology, 38(6), 632-645.
https://doi.org/10.1177/0960327119829518

Radić I, Mijović M, Tatalović NR, Mitić M, Lukić V, Joksimović B, Petrović Z, Ristić S, Veličković S, Nestorović V, Ćorac AM, Mirić M, Adžić M, Blagojević DP, Popović LM, Janićijević-Hudomal S. Protective effects of whey on rat liver damage induced by chronic alcohol intake. in Human and Experimental Toxicology. 2019;38(6):632-645.
doi:10.1177/0960327119829518 .

Radić, Ivan, Mijović, Milica, Tatalović, Nikola R., Mitić, Miloš, Lukić, Vera, Joksimović, Bojan, Petrović, Zorica, Ristić, Siniša, Veličković, Stefan, Nestorović, Vojkan, Ćorac, Aleksandar M., Mirić, Mirjana, Adžić, Miroslav, Blagojević, Duško P., Popović, Ljiljana M., Janićijević-Hudomal, Snežana, "Protective effects of whey on rat liver damage induced by chronic alcohol intake" in Human and Experimental Toxicology, 38, no. 6 (2019):632-645,
https://doi.org/10.1177/0960327119829518 . .

TY  - JOUR
AU  - Radić, Ivan
AU  - Nestorović, Vojkan
AU  - Mijović, Milica
AU  - Tatalović, Nikola R.
AU  - Joksimović, Bojan
AU  - Lukić, Vera
AU  - Mitić, Miloš
AU  - Adžić, Miroslav
AU  - Blagojević, Duško P.
AU  - Veličković, Stefan
AU  - Bulajić, Sonja
AU  - Đerković, Branislav
AU  - Mirić, Mirjana
AU  - Janićijević-Hudomal, Snežana
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7931
AB  - We studied the effects of whey and pumpkin seed oil supplementation on the biochemical parameters in blood serum of male rats after chronic ad libitum alcohol consumption. The levels of AST, ALT, total bilirubin, ALP, LDH, triglycerides, total cholesterol, HDL, LDL, VLDL, triglyceride/HDL ratio, total cholesterol/HDL ratio (cholesterol ratio) and LDL/HDL ratio (index of atherosclerosis) were determined in rats after six weeks of treatment with: (i) ethanol (12% ethanol, ad libitum), (ii) whey (2 g/kg per day), (iii) pumpkin seed oil (2 mL/kg per day), (iv) both ethanol and whey, and (v) both ethanol and pumpkin seed oil. The results showed no changes in the levels of AST, ALT, total bilirubin, ALP, total cholesterol, HDL and VLDL in alcoholic rats when compared to the controls (fed with a standard laboratory diet ad libitum) and rats supplemented with whey and pumpkin seed oil. Our results suggest that alcohol consumption in small doses for 6 weeks changes lipid metabolism and significantly elevates the LDL/HDL ratio (index of atherosclerosis) but does not induce extensive liver damage. Ethanol consumption in our experimental conditions lowered the triglyceride level as well as the triglyceride/HDL ratio, suggesting lipid redistribution and the induction of some cardio-protective effect. However, ethanol induced a higher index of atherosclerosis. Pumpkin seed oil showed some protective potential in alcoholic rats by lowering the total cholesterol/HDL ratio, but it elevated the LDH. Whey consumption prevented elevation of the atherosclerosis index, pointing to its protective role, probably through the redistribution of lipids. However, whey in combination with ethanol elevated LDH.
T2  - Archives of Biological Sciences
T1  - The effects of whey and pumpkin seed oil on blood biochemical parameters of liver function and lipid profile in rats chronically drinking low concentrations of ethanol
VL  - 70
IS  - 3
SP  - 531
EP  - 541
DO  - 10.2298/ABS180320014R
ER  - 

@article{
author = "Radić, Ivan and Nestorović, Vojkan and Mijović, Milica and Tatalović, Nikola R. and Joksimović, Bojan and Lukić, Vera and Mitić, Miloš and Adžić, Miroslav and Blagojević, Duško P. and Veličković, Stefan and Bulajić, Sonja and Đerković, Branislav and Mirić, Mirjana and Janićijević-Hudomal, Snežana",
year = "2018",
abstract = "We studied the effects of whey and pumpkin seed oil supplementation on the biochemical parameters in blood serum of male rats after chronic ad libitum alcohol consumption. The levels of AST, ALT, total bilirubin, ALP, LDH, triglycerides, total cholesterol, HDL, LDL, VLDL, triglyceride/HDL ratio, total cholesterol/HDL ratio (cholesterol ratio) and LDL/HDL ratio (index of atherosclerosis) were determined in rats after six weeks of treatment with: (i) ethanol (12% ethanol, ad libitum), (ii) whey (2 g/kg per day), (iii) pumpkin seed oil (2 mL/kg per day), (iv) both ethanol and whey, and (v) both ethanol and pumpkin seed oil. The results showed no changes in the levels of AST, ALT, total bilirubin, ALP, total cholesterol, HDL and VLDL in alcoholic rats when compared to the controls (fed with a standard laboratory diet ad libitum) and rats supplemented with whey and pumpkin seed oil. Our results suggest that alcohol consumption in small doses for 6 weeks changes lipid metabolism and significantly elevates the LDL/HDL ratio (index of atherosclerosis) but does not induce extensive liver damage. Ethanol consumption in our experimental conditions lowered the triglyceride level as well as the triglyceride/HDL ratio, suggesting lipid redistribution and the induction of some cardio-protective effect. However, ethanol induced a higher index of atherosclerosis. Pumpkin seed oil showed some protective potential in alcoholic rats by lowering the total cholesterol/HDL ratio, but it elevated the LDH. Whey consumption prevented elevation of the atherosclerosis index, pointing to its protective role, probably through the redistribution of lipids. However, whey in combination with ethanol elevated LDH.",
journal = "Archives of Biological Sciences",
title = "The effects of whey and pumpkin seed oil on blood biochemical parameters of liver function and lipid profile in rats chronically drinking low concentrations of ethanol",
volume = "70",
number = "3",
pages = "531-541",
doi = "10.2298/ABS180320014R"
}

Radić, I., Nestorović, V., Mijović, M., Tatalović, N. R., Joksimović, B., Lukić, V., Mitić, M., Adžić, M., Blagojević, D. P., Veličković, S., Bulajić, S., Đerković, B., Mirić, M.,& Janićijević-Hudomal, S.. (2018). The effects of whey and pumpkin seed oil on blood biochemical parameters of liver function and lipid profile in rats chronically drinking low concentrations of ethanol. in Archives of Biological Sciences, 70(3), 531-541.
https://doi.org/10.2298/ABS180320014R

Radić I, Nestorović V, Mijović M, Tatalović NR, Joksimović B, Lukić V, Mitić M, Adžić M, Blagojević DP, Veličković S, Bulajić S, Đerković B, Mirić M, Janićijević-Hudomal S. The effects of whey and pumpkin seed oil on blood biochemical parameters of liver function and lipid profile in rats chronically drinking low concentrations of ethanol. in Archives of Biological Sciences. 2018;70(3):531-541.
doi:10.2298/ABS180320014R .

Radić, Ivan, Nestorović, Vojkan, Mijović, Milica, Tatalović, Nikola R., Joksimović, Bojan, Lukić, Vera, Mitić, Miloš, Adžić, Miroslav, Blagojević, Duško P., Veličković, Stefan, Bulajić, Sonja, Đerković, Branislav, Mirić, Mirjana, Janićijević-Hudomal, Snežana, "The effects of whey and pumpkin seed oil on blood biochemical parameters of liver function and lipid profile in rats chronically drinking low concentrations of ethanol" in Archives of Biological Sciences, 70, no. 3 (2018):531-541,
https://doi.org/10.2298/ABS180320014R . .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Brkić, Željka
AU  - Mitić, Miloš
AU  - Francija, Ester
AU  - Jovičić, Milica J.
AU  - Radulović, Jelena
AU  - Marić, Nađa P.
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1939
AB  - Background: Mounting evidence demonstrates enhanced systemic levels of inflammatory mediators in depression, indicating that inflammation may play a role in the etiology and course of mood disorders. Indeed, proinflammatory cytokines induce a behavioral state of conservation- withdrawal resembling human depression, characterized by negative mood, fatigue, anhedonia, psychomotor retardation, loss of appetite, and cognitive deficits. Neuroinflammation also contributes to non-responsiveness to current antidepressant (AD) therapies. Namely, response to conventional AD medications is associated with a decrease in inflammatory biomarkers, whereas resistance to treatment is accompanied by increased inflammation. Methods: In this review, we will discuss the utility and shortcomings of pharmacologic AD treatment strategies focused on inflammatory pathways, applied alone or as an adjuvant component to current AD therapies. Results: Mechanisms of cytokine actions on behavior involve activation of inflammatory pathways in the brain, resulting in changes of neurotransmitter metabolism, neuroendocrine function, and neuronal plasticity. Selective serotonin reuptake inhibitors exhibit the most beneficial effects in restraining the inflammation markers in depression. Different anti-inflammatory agents exhibit AD effects via modulating neurotransmitter systems, neuroplasticity markers and glucocorticoid receptor signaling. Anti-inflammatory add-on therapy in depression highlights such treatment as a candidate for enhancement strategy in patients with moderate-to-severe depression. Conclusion: The interactions between the immune system and CNS are not only involved in shaping behavior, but also in responding to therapeutics. Even though, substantial evidence from animal and human research support a beneficial effect of anti-inflammatory add-on therapy in depression, further research with special attention on safety, particularly during prolonged periods of antiinflammatory co-treatments, is required.
T2  - Current Neuropharmacology
T1  - Therapeutic Strategies for Treatment of Inflammation-related Depression
VL  - 16
IS  - 2
SP  - 176
EP  - 209
DO  - 10.2174/1570159X15666170828163048
ER  - 

@article{
author = "Adžić, Miroslav and Brkić, Željka and Mitić, Miloš and Francija, Ester and Jovičić, Milica J. and Radulović, Jelena and Marić, Nađa P.",
year = "2018",
abstract = "Background: Mounting evidence demonstrates enhanced systemic levels of inflammatory mediators in depression, indicating that inflammation may play a role in the etiology and course of mood disorders. Indeed, proinflammatory cytokines induce a behavioral state of conservation- withdrawal resembling human depression, characterized by negative mood, fatigue, anhedonia, psychomotor retardation, loss of appetite, and cognitive deficits. Neuroinflammation also contributes to non-responsiveness to current antidepressant (AD) therapies. Namely, response to conventional AD medications is associated with a decrease in inflammatory biomarkers, whereas resistance to treatment is accompanied by increased inflammation. Methods: In this review, we will discuss the utility and shortcomings of pharmacologic AD treatment strategies focused on inflammatory pathways, applied alone or as an adjuvant component to current AD therapies. Results: Mechanisms of cytokine actions on behavior involve activation of inflammatory pathways in the brain, resulting in changes of neurotransmitter metabolism, neuroendocrine function, and neuronal plasticity. Selective serotonin reuptake inhibitors exhibit the most beneficial effects in restraining the inflammation markers in depression. Different anti-inflammatory agents exhibit AD effects via modulating neurotransmitter systems, neuroplasticity markers and glucocorticoid receptor signaling. Anti-inflammatory add-on therapy in depression highlights such treatment as a candidate for enhancement strategy in patients with moderate-to-severe depression. Conclusion: The interactions between the immune system and CNS are not only involved in shaping behavior, but also in responding to therapeutics. Even though, substantial evidence from animal and human research support a beneficial effect of anti-inflammatory add-on therapy in depression, further research with special attention on safety, particularly during prolonged periods of antiinflammatory co-treatments, is required.",
journal = "Current Neuropharmacology",
title = "Therapeutic Strategies for Treatment of Inflammation-related Depression",
volume = "16",
number = "2",
pages = "176-209",
doi = "10.2174/1570159X15666170828163048"
}

Adžić, M., Brkić, Ž., Mitić, M., Francija, E., Jovičić, M. J., Radulović, J.,& Marić, N. P.. (2018). Therapeutic Strategies for Treatment of Inflammation-related Depression. in Current Neuropharmacology, 16(2), 176-209.
https://doi.org/10.2174/1570159X15666170828163048

Adžić M, Brkić Ž, Mitić M, Francija E, Jovičić MJ, Radulović J, Marić NP. Therapeutic Strategies for Treatment of Inflammation-related Depression. in Current Neuropharmacology. 2018;16(2):176-209.
doi:10.2174/1570159X15666170828163048 .

Adžić, Miroslav, Brkić, Željka, Mitić, Miloš, Francija, Ester, Jovičić, Milica J., Radulović, Jelena, Marić, Nađa P., "Therapeutic Strategies for Treatment of Inflammation-related Depression" in Current Neuropharmacology, 16, no. 2 (2018):176-209,
https://doi.org/10.2174/1570159X15666170828163048 . .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Mitić, Miloš
AU  - Radoičić, Marija B.
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1715
AB  - Depression is a disease of an abnormal brain energy metabolism also marked with increased apoptosis in specific brain regions. Mounting evidence indicates that the mitochondrial oxidative phosphorylation and apoptosis are novel targets for the actions of estrogen receptors (ERs). In this study, we examined the effects of antidepressant (AD) fluoxetine (FLU) treatment on the mitochondria] ER alpha (ER alpha), ER beta (total and phospho-pER(beta) and their association with cytochrome c (cyt oxidase activity and apoptotic Bcl2/Bax-molecules in the hippocampal mitochondria of chronically isolated (CPSI) female and male rats depicting depression. Impaired behaviour induced by CPSI was followed by decreased corticosterone (CORT) in both sexes and downregulation of cyt c oxidase in males. CPSI did not affect the ERa in either of sexes, but it decreased mitochondrial ER beta and increased pER beta in both sexes. Stress-reduced ER beta is associated with a decrease in mitochondrial energetic processes in males and with apoptotic mechanisms in females. FLU normalized behaviour in both sexes and increased cyt c oxidase in females. FLU elevated ERa in males, increased ER beta and decreased pERB in both sexes. The AD-induced alterations of ER beta paralleled with bioenergetics and pro-survival pathways in females. In conclusion, sex-unspecific regulation of ER beta by the stress and by AD and its differential convergence with bioenergetics and apoptotic pathways in females and males implies its role as a vulnerability factor in the stress response and emphasizes mitochondrial ER beta-dependent pathways as an important gateway of ADs action, at least in females. (C) 2017 Elsevier B.V. All rights reserved.
T2  - Brain Research
T1  - Mitochondrial estrogen receptors as a vulnerability factor of chronic stress and mediator of fluoxetine treatment in female and male rat hippocampus
VL  - 1671
SP  - 77
EP  - 84
DO  - 10.1016/j.brainres.2017.07.007
ER  - 

@article{
author = "Adžić, Miroslav and Mitić, Miloš and Radoičić, Marija B.",
year = "2017",
abstract = "Depression is a disease of an abnormal brain energy metabolism also marked with increased apoptosis in specific brain regions. Mounting evidence indicates that the mitochondrial oxidative phosphorylation and apoptosis are novel targets for the actions of estrogen receptors (ERs). In this study, we examined the effects of antidepressant (AD) fluoxetine (FLU) treatment on the mitochondria] ER alpha (ER alpha), ER beta (total and phospho-pER(beta) and their association with cytochrome c (cyt oxidase activity and apoptotic Bcl2/Bax-molecules in the hippocampal mitochondria of chronically isolated (CPSI) female and male rats depicting depression. Impaired behaviour induced by CPSI was followed by decreased corticosterone (CORT) in both sexes and downregulation of cyt c oxidase in males. CPSI did not affect the ERa in either of sexes, but it decreased mitochondrial ER beta and increased pER beta in both sexes. Stress-reduced ER beta is associated with a decrease in mitochondrial energetic processes in males and with apoptotic mechanisms in females. FLU normalized behaviour in both sexes and increased cyt c oxidase in females. FLU elevated ERa in males, increased ER beta and decreased pERB in both sexes. The AD-induced alterations of ER beta paralleled with bioenergetics and pro-survival pathways in females. In conclusion, sex-unspecific regulation of ER beta by the stress and by AD and its differential convergence with bioenergetics and apoptotic pathways in females and males implies its role as a vulnerability factor in the stress response and emphasizes mitochondrial ER beta-dependent pathways as an important gateway of ADs action, at least in females. (C) 2017 Elsevier B.V. All rights reserved.",
journal = "Brain Research",
title = "Mitochondrial estrogen receptors as a vulnerability factor of chronic stress and mediator of fluoxetine treatment in female and male rat hippocampus",
volume = "1671",
pages = "77-84",
doi = "10.1016/j.brainres.2017.07.007"
}

Adžić, M., Mitić, M.,& Radoičić, M. B.. (2017). Mitochondrial estrogen receptors as a vulnerability factor of chronic stress and mediator of fluoxetine treatment in female and male rat hippocampus. in Brain Research, 1671, 77-84.
https://doi.org/10.1016/j.brainres.2017.07.007

Adžić M, Mitić M, Radoičić MB. Mitochondrial estrogen receptors as a vulnerability factor of chronic stress and mediator of fluoxetine treatment in female and male rat hippocampus. in Brain Research. 2017;1671:77-84.
doi:10.1016/j.brainres.2017.07.007 .

Adžić, Miroslav, Mitić, Miloš, Radoičić, Marija B., "Mitochondrial estrogen receptors as a vulnerability factor of chronic stress and mediator of fluoxetine treatment in female and male rat hippocampus" in Brain Research, 1671 (2017):77-84,
https://doi.org/10.1016/j.brainres.2017.07.007 . .

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  - THES
AU  - Mitić, Miloš
PY  - 2017
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=5017
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:15687/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1025152434
UR  - http://nardus.mpn.gov.rs/123456789/8269
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7321
AB  - Smatra se da je hronični stres jedan od glavnih etioloških faktora povezanih sapatofiziologijom mnogih psihijatrijskih poremećaja, uključujući depresiju. Iako je odgovor nastres ključan u odrţavanju homeostaze, maladaptivni odgovor moţe dovesti do povećanjafaktora rizika koji dovode do razvoja bolesti. Tokom proteklih decenija brojne studijeizvedene na depresivnim pacijentima kao i istraţivanja na ţivotinjskim modelima predloţilesu nekoliko bioloških teorija koje su pokušale da objasne patogenezu depresivnih poremećajauzrokovanih stresom. Jedan od najkonzistentnijih nalaza u ovim istraţivanjima jeste narušenaaktivnost hipotalamo-hipofizno-adrenalne (HPA) ose, koja se odlikuje narušenom funkcijomglukokortikoidnog receptora (GR) pogotovu u hipokampusu, moţdanoj strukturi koja jenajosetlijivija na stres. Kao posledica gore pomenutih činjenica sasvim je logično sto je GRisplivao kao meta novih antidepresivnih lekova. Osim pitanja molekularne osnove upatogenezi depresije, poslednjih godina sve veću paţnju privlači pitanje polnog dimorfizma uodgovoru na stres i adekvatnu terapiju, s obzirom to da epidemiološke studije ukazuju da suţene podloţnije depresiji i da dva puta češće oboljevaju od iste. TakoĎe, brojne studijepokazuju i da ţene slabije odgovaraju na terapiju tricikličnim antidepresivima i da znatnobolji učinak kod ovog pola imaju antidepresivi iz klase selektivnih inhibitora ponovnog unosaserotonina (SSRI). Ipak, pored svih prikupljenih podataka molekularni mehanizmi koji leţe uosnovi ovih kliničkih nalaza, kao i molekularne osnove polnog dimorfizma u odgovoru nastres, uključujući glukokortikoide i signalizaciju posredovanu GR-om, još uvek nisu upotpunosti razjašnjeni.Pored glukokortikoida, vaţnu ulogu u regulaciji funkcije GR-a ima i njegovafosforilacija na specifičnim aminokiselinskim ostacima koja utiče na stabilnost samogreceptora i njegovu translokaciju iz citoplazme u jedro, što dovodi do pojačane ili smanjenetranskripcione aktivnosti samog GR-a, što sve zajedno utiče na vaţne ćelijske procese.Imajući u vidu vaţnost fosforilacije u regulaciji funkcije GR-a, kao i rezultate prethodnodobijene u našoj laboratoriji, u ovoj doktorskoj disertaciji ispitivan je polno-specifičan efekathroničnog tretmana fluoksetina, antidepresiva iz klase SSRI, na ponašanje nalik depresivnom,na koncentraciju kortikosterona (KORT) u serumu, unutar ćelijsku distribuciju GR-a, kao i nafosfo-forme receptora na serinu 232 (pGR232), serinu 246 (pGR246) i treoninu 171(pGR171) u hipokampusu ţenki i muţjaka pacova Wistar soja prethodno izloţenih stresuhronične socijalne izolacije...
AB  - Exposure to chronic stress has been associated with the pathophysiology of manypsychiatric disorders including depression. Although, the stress response is essential formaintenance of homeostasis, maladaptive response to stress can elevate risk factors that leadto the disease. Several theories have been proposed to explain stress-related pathogenesis ofdepression, including impaired activity of hypothalamo-pituitary-adrenal (HPA) axis, which isone of the most consistent findings in assessing the depressive state in years of research.Notably, studies carried out in depressed patients, as well as studies on animal models ofdepression showed consistently dysfunctional limbic LHPA axis activity, leading to alteredlevels of circulating glucocorticoids. The activity of LHPA axis is controlled throughinhibitory feedback mechanisms involving different brain structures with main research focuson hippocampus. At the molecular level, glucocorticoids exert their effects by activating theglucocorticoid receptor (GR), a key regulator of the negative feedback of the LHPA axisactivity. Therefore taking into account above mentioned facts it is quite logical that GRemerged as a potential candidate for antidepressant action.Aside from investigating the molecular mechanisms that lie in the basis of depression,in recent years the question of gender-dimorphism is becoming more appealing and attractsmore attention. Epidemiological studies demonstrate that women are more vulnerable to stressrelated psychopathologies than men, since depression occurs twice as frequently in women.Furthermore, women tend to show poorer response rates and slower clinical improvementwith tricyclic antidepressants (TCAs) and appear to respond better to selective serotoninreuptake inhibitors (SSRIs). However the mechanisms underlying these clinical facts, as wellas molecular specificities that underlie possible sex differences, including the GCs and GRsignaling are not well defined.Besides glucocorticoids, the GR activity could be also controlled by specificmodification via phosphorylation of GR on specific aminoacide residues that influence thestability of receptor and its translocation from cytoplasm to the nucleus which may lead toenhanced or diminished transcriptional activity of the GR, all together to affect multiplecellular processes...
PB  - Универзитет у Београду, Биолошки факултет
T2  - Универзитет у Београду
T1  - Polno specifičan efekat fluoksetina na signalizaciju posredovanu glukokortikoidnim receptorom u hipokampusu pacova izlaganih hroničnom stresu izolacije
UR  - https://hdl.handle.net/21.15107/rcub_nardus_8269
ER  - 

@phdthesis{
author = "Mitić, Miloš",
year = "2017",
abstract = "Smatra se da je hronični stres jedan od glavnih etioloških faktora povezanih sapatofiziologijom mnogih psihijatrijskih poremećaja, uključujući depresiju. Iako je odgovor nastres ključan u odrţavanju homeostaze, maladaptivni odgovor moţe dovesti do povećanjafaktora rizika koji dovode do razvoja bolesti. Tokom proteklih decenija brojne studijeizvedene na depresivnim pacijentima kao i istraţivanja na ţivotinjskim modelima predloţilesu nekoliko bioloških teorija koje su pokušale da objasne patogenezu depresivnih poremećajauzrokovanih stresom. Jedan od najkonzistentnijih nalaza u ovim istraţivanjima jeste narušenaaktivnost hipotalamo-hipofizno-adrenalne (HPA) ose, koja se odlikuje narušenom funkcijomglukokortikoidnog receptora (GR) pogotovu u hipokampusu, moţdanoj strukturi koja jenajosetlijivija na stres. Kao posledica gore pomenutih činjenica sasvim je logično sto je GRisplivao kao meta novih antidepresivnih lekova. Osim pitanja molekularne osnove upatogenezi depresije, poslednjih godina sve veću paţnju privlači pitanje polnog dimorfizma uodgovoru na stres i adekvatnu terapiju, s obzirom to da epidemiološke studije ukazuju da suţene podloţnije depresiji i da dva puta češće oboljevaju od iste. TakoĎe, brojne studijepokazuju i da ţene slabije odgovaraju na terapiju tricikličnim antidepresivima i da znatnobolji učinak kod ovog pola imaju antidepresivi iz klase selektivnih inhibitora ponovnog unosaserotonina (SSRI). Ipak, pored svih prikupljenih podataka molekularni mehanizmi koji leţe uosnovi ovih kliničkih nalaza, kao i molekularne osnove polnog dimorfizma u odgovoru nastres, uključujući glukokortikoide i signalizaciju posredovanu GR-om, još uvek nisu upotpunosti razjašnjeni.Pored glukokortikoida, vaţnu ulogu u regulaciji funkcije GR-a ima i njegovafosforilacija na specifičnim aminokiselinskim ostacima koja utiče na stabilnost samogreceptora i njegovu translokaciju iz citoplazme u jedro, što dovodi do pojačane ili smanjenetranskripcione aktivnosti samog GR-a, što sve zajedno utiče na vaţne ćelijske procese.Imajući u vidu vaţnost fosforilacije u regulaciji funkcije GR-a, kao i rezultate prethodnodobijene u našoj laboratoriji, u ovoj doktorskoj disertaciji ispitivan je polno-specifičan efekathroničnog tretmana fluoksetina, antidepresiva iz klase SSRI, na ponašanje nalik depresivnom,na koncentraciju kortikosterona (KORT) u serumu, unutar ćelijsku distribuciju GR-a, kao i nafosfo-forme receptora na serinu 232 (pGR232), serinu 246 (pGR246) i treoninu 171(pGR171) u hipokampusu ţenki i muţjaka pacova Wistar soja prethodno izloţenih stresuhronične socijalne izolacije..., Exposure to chronic stress has been associated with the pathophysiology of manypsychiatric disorders including depression. Although, the stress response is essential formaintenance of homeostasis, maladaptive response to stress can elevate risk factors that leadto the disease. Several theories have been proposed to explain stress-related pathogenesis ofdepression, including impaired activity of hypothalamo-pituitary-adrenal (HPA) axis, which isone of the most consistent findings in assessing the depressive state in years of research.Notably, studies carried out in depressed patients, as well as studies on animal models ofdepression showed consistently dysfunctional limbic LHPA axis activity, leading to alteredlevels of circulating glucocorticoids. The activity of LHPA axis is controlled throughinhibitory feedback mechanisms involving different brain structures with main research focuson hippocampus. At the molecular level, glucocorticoids exert their effects by activating theglucocorticoid receptor (GR), a key regulator of the negative feedback of the LHPA axisactivity. Therefore taking into account above mentioned facts it is quite logical that GRemerged as a potential candidate for antidepressant action.Aside from investigating the molecular mechanisms that lie in the basis of depression,in recent years the question of gender-dimorphism is becoming more appealing and attractsmore attention. Epidemiological studies demonstrate that women are more vulnerable to stressrelated psychopathologies than men, since depression occurs twice as frequently in women.Furthermore, women tend to show poorer response rates and slower clinical improvementwith tricyclic antidepressants (TCAs) and appear to respond better to selective serotoninreuptake inhibitors (SSRIs). However the mechanisms underlying these clinical facts, as wellas molecular specificities that underlie possible sex differences, including the GCs and GRsignaling are not well defined.Besides glucocorticoids, the GR activity could be also controlled by specificmodification via phosphorylation of GR on specific aminoacide residues that influence thestability of receptor and its translocation from cytoplasm to the nucleus which may lead toenhanced or diminished transcriptional activity of the GR, all together to affect multiplecellular processes...",
publisher = "Универзитет у Београду, Биолошки факултет",
journal = "Универзитет у Београду",
title = "Polno specifičan efekat fluoksetina na signalizaciju posredovanu glukokortikoidnim receptorom u hipokampusu pacova izlaganih hroničnom stresu izolacije",
url = "https://hdl.handle.net/21.15107/rcub_nardus_8269"
}

Mitić, M.. (2017). Polno specifičan efekat fluoksetina na signalizaciju posredovanu glukokortikoidnim receptorom u hipokampusu pacova izlaganih hroničnom stresu izolacije. in Универзитет у Београду
Универзитет у Београду, Биолошки факултет..
https://hdl.handle.net/21.15107/rcub_nardus_8269

Mitić M. Polno specifičan efekat fluoksetina na signalizaciju posredovanu glukokortikoidnim receptorom u hipokampusu pacova izlaganih hroničnom stresu izolacije. in Универзитет у Београду. 2017;.
https://hdl.handle.net/21.15107/rcub_nardus_8269 .

Mitić, Miloš, "Polno specifičan efekat fluoksetina na signalizaciju posredovanu glukokortikoidnim receptorom u hipokampusu pacova izlaganih hroničnom stresu izolacije" in Универзитет у Београду (2017),
https://hdl.handle.net/21.15107/rcub_nardus_8269 .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Brkić, Željka
AU  - Bulajić, Sonja
AU  - Mitić, Miloš
AU  - Radojčić, Marija
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1304
AB  - Mitochondria are cell organelles crucial to the production of cellular energy. Several lines of evidence have indicated that mitochondrial dysfunction could be related to the pathophysiology of CNS diseases including bipolar disorder, major depressive disorder, and schizophrenia. These changes include impaired energy metabolism in the brain, co-morbidity with mitochondrial diseases, the effects of psychotropics on mitochondrial function, increased mitochondrial DNA (mtDNA) deletion in the brain, and association with mtDNA polymorphisms. Additionally, psychotropic drug treatments can alter energy metabolism and may affect mitochondrial processes. This review focuses on recent findings regarding the effects of antidepressants on mitochondrial processes in psychiatric disorders. Drug Dev Res 77 : 400-406, 2016. (c) 2016 Wiley Periodicals, Inc.
T2  - Drug Development Research
T1  - Antidepressant Action on Mitochondrial Dysfunction in Psychiatric Disorders
VL  - 77
IS  - 7
SP  - 400
EP  - 406
DO  - 10.1002/ddr.21332
ER  - 

@article{
author = "Adžić, Miroslav and Brkić, Željka and Bulajić, Sonja and Mitić, Miloš and Radojčić, Marija",
year = "2016",
abstract = "Mitochondria are cell organelles crucial to the production of cellular energy. Several lines of evidence have indicated that mitochondrial dysfunction could be related to the pathophysiology of CNS diseases including bipolar disorder, major depressive disorder, and schizophrenia. These changes include impaired energy metabolism in the brain, co-morbidity with mitochondrial diseases, the effects of psychotropics on mitochondrial function, increased mitochondrial DNA (mtDNA) deletion in the brain, and association with mtDNA polymorphisms. Additionally, psychotropic drug treatments can alter energy metabolism and may affect mitochondrial processes. This review focuses on recent findings regarding the effects of antidepressants on mitochondrial processes in psychiatric disorders. Drug Dev Res 77 : 400-406, 2016. (c) 2016 Wiley Periodicals, Inc.",
journal = "Drug Development Research",
title = "Antidepressant Action on Mitochondrial Dysfunction in Psychiatric Disorders",
volume = "77",
number = "7",
pages = "400-406",
doi = "10.1002/ddr.21332"
}

Adžić, M., Brkić, Ž., Bulajić, S., Mitić, M.,& Radojčić, M.. (2016). Antidepressant Action on Mitochondrial Dysfunction in Psychiatric Disorders. in Drug Development Research, 77(7), 400-406.
https://doi.org/10.1002/ddr.21332

Adžić M, Brkić Ž, Bulajić S, Mitić M, Radojčić M. Antidepressant Action on Mitochondrial Dysfunction in Psychiatric Disorders. in Drug Development Research. 2016;77(7):400-406.
doi:10.1002/ddr.21332 .

Adžić, Miroslav, Brkić, Željka, Bulajić, Sonja, Mitić, Miloš, Radojčić, Marija, "Antidepressant Action on Mitochondrial Dysfunction in Psychiatric Disorders" in Drug Development Research, 77, no. 7 (2016):400-406,
https://doi.org/10.1002/ddr.21332 . .

TY  - JOUR
AU  - Brkić, Željka
AU  - Petrović, Zorica D.
AU  - Franić, Dušanka
AU  - Mitić, Miloš
AU  - Adžić, Miroslav
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1218
AB  - Inflammation plays a key role in the pathogenesis of major depressive disorder (MDD) for a subset of depressed individuals. One of the possible routes by which cytokines can induce depressive symptoms is by promoting the dysregulation of hypothalamic-pituitary-adrenal (HPA) axis via altering glucocorticoid receptor (GR) function. We investigated the mechanisms that finely tune the GR functioning upon lipopolysaccharide (LPS), i.e., subcellular localization of the GR, the levels of its co-chaperones FK506 binding protein 52 (FKBP4) and FK506 binding protein 51 (FKBP5), the receptor phosphorylation status along with its upstream kinases, as well as mRNA levels of GR-regulated genes in the prefrontal cortex (PFC) of male and female Wistar rats. We found that upon LPS treatment, animals of both sexes exhibited depressive-like behavior and elevated serum corticosterone. However, the nuclear translocation of the GR and both FKBPs was found only in males, together with elevated phosphorylation of the GR at serine 232 and 246 and the activation and nuclear translocation of all analyzed kinases. This activation of the GR in males was paralleled with altered expression of GR-related genes, particularly PTGS2 and BDNF. Our data suggest that LPS treatment produced alterations in the mechanisms that control the GR nuclear translocation in the PFC of males, and that these mechanisms may contribute to the sex-specific dysfunction of GR-related neurotrophic and neuroinflammatory processes in inflammation-associated depression.
T2  - Psychopharmacology
T1  - Male-specific effects of lipopolysaccharide on glucocorticoid receptor nuclear translocation in the prefrontal cortex of depressive rats
VL  - 233
IS  - 18
SP  - 3315
EP  - 3330
DO  - 10.1007/s00213-016-4374-y
ER  - 

@article{
author = "Brkić, Željka and Petrović, Zorica D. and Franić, Dušanka and Mitić, Miloš and Adžić, Miroslav",
year = "2016",
abstract = "Inflammation plays a key role in the pathogenesis of major depressive disorder (MDD) for a subset of depressed individuals. One of the possible routes by which cytokines can induce depressive symptoms is by promoting the dysregulation of hypothalamic-pituitary-adrenal (HPA) axis via altering glucocorticoid receptor (GR) function. We investigated the mechanisms that finely tune the GR functioning upon lipopolysaccharide (LPS), i.e., subcellular localization of the GR, the levels of its co-chaperones FK506 binding protein 52 (FKBP4) and FK506 binding protein 51 (FKBP5), the receptor phosphorylation status along with its upstream kinases, as well as mRNA levels of GR-regulated genes in the prefrontal cortex (PFC) of male and female Wistar rats. We found that upon LPS treatment, animals of both sexes exhibited depressive-like behavior and elevated serum corticosterone. However, the nuclear translocation of the GR and both FKBPs was found only in males, together with elevated phosphorylation of the GR at serine 232 and 246 and the activation and nuclear translocation of all analyzed kinases. This activation of the GR in males was paralleled with altered expression of GR-related genes, particularly PTGS2 and BDNF. Our data suggest that LPS treatment produced alterations in the mechanisms that control the GR nuclear translocation in the PFC of males, and that these mechanisms may contribute to the sex-specific dysfunction of GR-related neurotrophic and neuroinflammatory processes in inflammation-associated depression.",
journal = "Psychopharmacology",
title = "Male-specific effects of lipopolysaccharide on glucocorticoid receptor nuclear translocation in the prefrontal cortex of depressive rats",
volume = "233",
number = "18",
pages = "3315-3330",
doi = "10.1007/s00213-016-4374-y"
}

Brkić, Ž., Petrović, Z. D., Franić, D., Mitić, M.,& Adžić, M.. (2016). Male-specific effects of lipopolysaccharide on glucocorticoid receptor nuclear translocation in the prefrontal cortex of depressive rats. in Psychopharmacology, 233(18), 3315-3330.
https://doi.org/10.1007/s00213-016-4374-y

Brkić Ž, Petrović ZD, Franić D, Mitić M, Adžić M. Male-specific effects of lipopolysaccharide on glucocorticoid receptor nuclear translocation in the prefrontal cortex of depressive rats. in Psychopharmacology. 2016;233(18):3315-3330.
doi:10.1007/s00213-016-4374-y .

Brkić, Željka, Petrović, Zorica D., Franić, Dušanka, Mitić, Miloš, Adžić, Miroslav, "Male-specific effects of lipopolysaccharide on glucocorticoid receptor nuclear translocation in the prefrontal cortex of depressive rats" in Psychopharmacology, 233, no. 18 (2016):3315-3330,
https://doi.org/10.1007/s00213-016-4374-y . .

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 . .