Mitić, Miloš

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  • Mitić, Miloš (41)

Author's Bibliography

Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease

Ivković, Sanja; Major, Tamara; Mitić, Miloš; Lončarević-Vasiljković, Nataša; Jović, Milena; Adžić, Miroslav

(2022)

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 . .
7

Hallucinogenic drugs and their potential for treating fear-related disorders: Through the lens of fear extinction

Glavonić, Emilija; Mitić, Miloš; Adžić, Miroslav

(2022)

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
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",
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.
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;.
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 (2022),
https://doi.org/10.1002/jnr.25017 . .
3
1

Does the application of acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease lead to depression?

Mitić, Miloš; Lazarević-Pašti, Tamara

(2021)

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 . .
10
7
3
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Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption

Radić, Ivan; Mirić, Mirjana; Mijović, Milica; Tatalović, Nikola; Mitić, Miloš; Nestorović, Vojkan; Adžić, Miroslav; Blagojević, Duško; Popović, Ljiljana; Janićijević-Hudomal, Snežana

(2021)

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 . .

Protective effects of whey on rat liver damage induced by chronic alcohol intake

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

(2019)

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 & 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 & 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 & 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 & 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 & Experimental Toxicology, 38, no. 6 (2019):632-645,
https://doi.org/10.1177/0960327119829518 . .
3
4
3

Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression

Francija, Ester; Petrović, Zorica; Brkić, Željka; Mitić, Miloš; Radulović, Jelena; Adžić, Miroslav

(2019)

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 . .
1
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14
16

Glucocorticoid receptor alpha translational isoforms as mediators of early adversities and negative emotional states

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.

(2019)

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 . .
1
2
1
1

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

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

(2018)

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  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46641800014R
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 . .
2
1
2

Therapeutic Strategies for Treatment of Inflammation-related Depression

Adžić, Miroslav; Brkić, Željka; Mitić, Miloš; Francija, Ester; Jovicic, Milica J.; Radulovic, Jelena; Maric, Nadja P.

(2018)

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Brkić, Željka
AU  - Mitić, Miloš
AU  - Francija, Ester
AU  - Jovicic, Milica J.
AU  - Radulovic, Jelena
AU  - Maric, Nadja 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 Jovicic, Milica J. and Radulovic, Jelena and Maric, Nadja 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., Jovicic, M. J., Radulovic, J.,& Maric, 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, Jovicic MJ, Radulovic J, Maric 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, Jovicic, Milica J., Radulovic, Jelena, Maric, Nadja P., "Therapeutic Strategies for Treatment of Inflammation-related Depression" in Current Neuropharmacology, 16, no. 2 (2018):176-209,
https://doi.org/10.2174/1570159X15666170828163048 . .
1
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Polno specifičan efekat fluoksetina na signalizaciju posredovanu glukokortikoidnim receptorom u hipokampusu pacova izlaganih hroničnom stresu izolacije

Mitić, Miloš

(Универзитет у Београду, Биолошки факултет, 2017)

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 .

Distinct modifications of hippocampal glucocorticoid receptor phosphorylation and FKBPs by lipopolysaccharide in depressive female and male rats

Brkić, Željka; Francija, Ester; Petrović, Zorica D.; Franić, Dušanka; Lukić, Iva; Mitić, Miloš; Adžić, Miroslav

(2017)

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 . .
10
7
7

Convergence of glycogen synthase kinase 3 beta and GR signaling in response to fluoxetine treatment in chronically stressed female and male rats

Mitić, Miloš; Brkić, Željka; Lukić, Iva; Adžić, Miroslav

(2017)

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 . .

Mitochondrial estrogen receptors as a vulnerability factor of chronic stress and mediator of fluoxetine treatment in female and male rat hippocampus

Adžić, Miroslav; Mitić, Miloš; Radoičić, Marija B.

(2017)

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 . .
1
12
11
11

Antidepressant Action on Mitochondrial Dysfunction in Psychiatric Disorders

Adžić, Miroslav; Brkić, Željka; Bulajić, Sonja; Mitić, Miloš; Radoičić, Marija B.

(2016)

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Brkić, Željka
AU  - Bulajić, Sonja
AU  - Mitić, Miloš
AU  - Radoičić, Marija B.
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 Radoičić, Marija B.",
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.,& Radoičić, M. B.. (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, Radoičić MB. 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, Radoičić, Marija B., "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 . .
11
40
32
37

Male-specific effects of lipopolysaccharide on glucocorticoid receptor nuclear translocation in the prefrontal cortex of depressive rats

Brkić, Željka; Petrović, Zorica D.; Franić, Dušanka; Mitić, Miloš; Adžić, Miroslav

(2016)

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 . .
9
8
8

Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress

Đorđević, Jelena D.; Đorđević, Ana D.; Adžić, Miroslav; Mitić, Miloš; Lukić, Iva; Radoičić, Marija B.

(2015)

TY  - JOUR
AU  - Đorđević, Jelena D.
AU  - Đorđević, Ana D.
AU  - Adžić, Miroslav
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Radoičić, 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 Radoičić, 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.,& Radoičić, 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, Radoičić 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, Radoičić, 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 . .
48
45
50

Effects of Female Gonadal Hormones and Lps on Depressive-Like Behavior in Rats

Mitić, Miloš; Lukić, Iva; Božović, Natalija; Đorđević, Jelena D.; Adžić, Miroslav

(2015)

TY  - JOUR
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Božović, Natalija
AU  - Đorđević, Jelena D.
AU  - Adžić, Miroslav
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/861
AB  - Considerable evidence shows an association of depression with the immune system and emphasizes the importance of gender in the etiology of the disease and the response to inflammatory stimuli. We examined the influence of immune-challenged systems on depressive-like behavior in female rats in the context of gonadal hormones. We used a neuroinflammatory model of depression elicited by lipopolysaccharide (LPS) administration on naive and ovariectomized (OVX) female rats, and examined the effects of estradiol (E2) and/or progesterone (P4) replacement therapy on animal behavior, as assessed by the forced swimming test (FST). We found that LPS and OVX increase immobility in the FST, while LPS also decreased body weight in naive female rats. Further, even though P4 application alone showed beneficial effects on the behavioral profile (it reduced immobility and increased climbing), supplementation of both hormones (E2 and P4) together to OVX rats failed to do so. When OVX rats were exposed to LPS-induced immune challenge, neither hormone individually nor their combination had any effect on immobility, however, their joint supplementation increased climbing behavior. In conclusion, our study confirmed that both LPS and OVX induced depressive-like behavior in female rats. Furthermore, our results potentiate P4 supplementation in relieving the depressive-like symptomatology in OVX rats, most likely through fine-tuning of different neurotransmitter systems. In the context of an activated immune system, the application of E2 and/or P4 does not provide any advantageous effects on depressive-like behavior.
T2  - Archives of biological sciences
T1  - Effects of Female Gonadal Hormones and Lps on Depressive-Like Behavior in Rats
VL  - 67
IS  - 3
SP  - 1025
EP  - 1032
DO  - 10.2298/ABS150130065M
ER  - 
@article{
author = "Mitić, Miloš and Lukić, Iva and Božović, Natalija and Đorđević, Jelena D. and Adžić, Miroslav",
year = "2015",
abstract = "Considerable evidence shows an association of depression with the immune system and emphasizes the importance of gender in the etiology of the disease and the response to inflammatory stimuli. We examined the influence of immune-challenged systems on depressive-like behavior in female rats in the context of gonadal hormones. We used a neuroinflammatory model of depression elicited by lipopolysaccharide (LPS) administration on naive and ovariectomized (OVX) female rats, and examined the effects of estradiol (E2) and/or progesterone (P4) replacement therapy on animal behavior, as assessed by the forced swimming test (FST). We found that LPS and OVX increase immobility in the FST, while LPS also decreased body weight in naive female rats. Further, even though P4 application alone showed beneficial effects on the behavioral profile (it reduced immobility and increased climbing), supplementation of both hormones (E2 and P4) together to OVX rats failed to do so. When OVX rats were exposed to LPS-induced immune challenge, neither hormone individually nor their combination had any effect on immobility, however, their joint supplementation increased climbing behavior. In conclusion, our study confirmed that both LPS and OVX induced depressive-like behavior in female rats. Furthermore, our results potentiate P4 supplementation in relieving the depressive-like symptomatology in OVX rats, most likely through fine-tuning of different neurotransmitter systems. In the context of an activated immune system, the application of E2 and/or P4 does not provide any advantageous effects on depressive-like behavior.",
journal = "Archives of biological sciences",
title = "Effects of Female Gonadal Hormones and Lps on Depressive-Like Behavior in Rats",
volume = "67",
number = "3",
pages = "1025-1032",
doi = "10.2298/ABS150130065M"
}
Mitić, M., Lukić, I., Božović, N., Đorđević, J. D.,& Adžić, M.. (2015). Effects of Female Gonadal Hormones and Lps on Depressive-Like Behavior in Rats. in Archives of biological sciences, 67(3), 1025-1032.
https://doi.org/10.2298/ABS150130065M
Mitić M, Lukić I, Božović N, Đorđević JD, Adžić M. Effects of Female Gonadal Hormones and Lps on Depressive-Like Behavior in Rats. in Archives of biological sciences. 2015;67(3):1025-1032.
doi:10.2298/ABS150130065M .
Mitić, Miloš, Lukić, Iva, Božović, Natalija, Đorđević, Jelena D., Adžić, Miroslav, "Effects of Female Gonadal Hormones and Lps on Depressive-Like Behavior in Rats" in Archives of biological sciences, 67, no. 3 (2015):1025-1032,
https://doi.org/10.2298/ABS150130065M . .
1
1
1

The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-beta

Adžić, Miroslav; Đorđević, Jelena D.; Mitić, Miloš; Brkić, Željka; Lukić, Iva; Radoičić, Marija B.

(2015)

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Đorđević, Jelena D.
AU  - Mitić, Miloš
AU  - Brkić, Željka
AU  - Lukić, Iva
AU  - Radoičić, Marija B.
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/670
AB  - Peripheral inflammation induced by lipopolysaccharide (LPS) causes behavioural changes indicative for depression. The possible mechanisms involve the interference with neuroinflammatory, neuroendocrine, and neurotrophic processes. Apart from heterogeneity in the molecular background, sexual context may be another factor relevant to the manifestation of mood disturbances upon an immune challenge. We investigated sex-dependent effects of a 7-day LPS treatment of adult Wistar rats on depressive-like behaviour and their relation with hypothalamic neuroendocrine factor, corticotrophin-releasing hormone (CRH), proplastic brain-derived neurotropic factor (BDNF), pro-inflammatory cyclooxygenase-2 (COX-2) and nuclear factor kappa beta (NFkB). Also, their regulators, the glucocorticoid receptor (GR) and CCAAT enhancer-binding protein (C/EBP) beta were followed. LPS induced depressive-like behaviour in females was associated with the increased hypothalamic CRH and decreased BDNF, but not with COX-2. These changes were paralleled by an increase in nuclear GR, NFkB and 20 kDa C/EBP beta. LPS also altered behaviour in males and increased CRH expression, but in contrast to females, this was accompanied with the elevated COX-2, accumulation of cytosolic GR and elevated nuclear 38 kDa C/EBP beta and NFkB. In conclusion, depressive-like phenotype induced by LPS in both sexes emerges from similar HPA axis activation and sex-specific alterations of hypothalamic molecular signalling: in males it is related to compromised control of neuroinflamation connected with cytoplasmic GR retention, while in females it is related to diminished proplastic capacity of BDNF. Sex-dependent mechanisms by which inflammation alters hypothalamic processes and cause pathological behaviour in animals, could be operative in the treatment of depression-related brain inflammation. (C) 2015 Elsevier B.V. All rights reserved.
T2  - Behavioural Brain Research
T1  - The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-beta
VL  - 291
SP  - 130
EP  - 139
DO  - 10.1016/j.bbr.2015.05.029
ER  - 
@article{
author = "Adžić, Miroslav and Đorđević, Jelena D. and Mitić, Miloš and Brkić, Željka and Lukić, Iva and Radoičić, Marija B.",
year = "2015",
abstract = "Peripheral inflammation induced by lipopolysaccharide (LPS) causes behavioural changes indicative for depression. The possible mechanisms involve the interference with neuroinflammatory, neuroendocrine, and neurotrophic processes. Apart from heterogeneity in the molecular background, sexual context may be another factor relevant to the manifestation of mood disturbances upon an immune challenge. We investigated sex-dependent effects of a 7-day LPS treatment of adult Wistar rats on depressive-like behaviour and their relation with hypothalamic neuroendocrine factor, corticotrophin-releasing hormone (CRH), proplastic brain-derived neurotropic factor (BDNF), pro-inflammatory cyclooxygenase-2 (COX-2) and nuclear factor kappa beta (NFkB). Also, their regulators, the glucocorticoid receptor (GR) and CCAAT enhancer-binding protein (C/EBP) beta were followed. LPS induced depressive-like behaviour in females was associated with the increased hypothalamic CRH and decreased BDNF, but not with COX-2. These changes were paralleled by an increase in nuclear GR, NFkB and 20 kDa C/EBP beta. LPS also altered behaviour in males and increased CRH expression, but in contrast to females, this was accompanied with the elevated COX-2, accumulation of cytosolic GR and elevated nuclear 38 kDa C/EBP beta and NFkB. In conclusion, depressive-like phenotype induced by LPS in both sexes emerges from similar HPA axis activation and sex-specific alterations of hypothalamic molecular signalling: in males it is related to compromised control of neuroinflamation connected with cytoplasmic GR retention, while in females it is related to diminished proplastic capacity of BDNF. Sex-dependent mechanisms by which inflammation alters hypothalamic processes and cause pathological behaviour in animals, could be operative in the treatment of depression-related brain inflammation. (C) 2015 Elsevier B.V. All rights reserved.",
journal = "Behavioural Brain Research",
title = "The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-beta",
volume = "291",
pages = "130-139",
doi = "10.1016/j.bbr.2015.05.029"
}
Adžić, M., Đorđević, J. D., Mitić, M., Brkić, Ž., Lukić, I.,& Radoičić, M. B.. (2015). The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-beta. in Behavioural Brain Research, 291, 130-139.
https://doi.org/10.1016/j.bbr.2015.05.029
Adžić M, Đorđević JD, Mitić M, Brkić Ž, Lukić I, Radoičić MB. The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-beta. in Behavioural Brain Research. 2015;291:130-139.
doi:10.1016/j.bbr.2015.05.029 .
Adžić, Miroslav, Đorđević, Jelena D., Mitić, Miloš, Brkić, Željka, Lukić, Iva, Radoičić, Marija B., "The contribution of hypothalamic neuroendocrine, neuroplastic and neuroinflammatory processes to lipopolysaccharide-induced depressive-like behaviour in female and male rats: Involvement of glucocorticoid receptor and C/EBP-beta" in Behavioural Brain Research, 291 (2015):130-139,
https://doi.org/10.1016/j.bbr.2015.05.029 . .
46
42
45

Maternal Deprivation of Rat Pups Reduces Body Weight and Alters Behavior in Adulthood in a Gender-Specific Manner

Đorđević, Jelena D.; Mitić, Miloš; Lukić, Iva; Adžić, Miroslav

(2015)

TY  - JOUR
AU  - Đorđević, Jelena D.
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Adžić, Miroslav
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/477
AB  - The early postnatal environment is critical for its capacity to influence adult behavior, and is associated with traits of altered physiological and neurobiological function and long-term predisposition to depression. Here we describe the delayed effects of maternal deprivation (MD) in male and female Wistar pups on their physical development and behavior in adulthood in tasks designed to explore depressive-like (forced swimming test, FST), and anxiety-like behaviors (elevated plus maze, EPM). We observed that MD led to reduced body weight in adulthood, anxiety-like traits in the EPM test and increased activity in the phases of the FST. Particularly, a consistent sexual dimorphism was observed in the responses to MD. A lower increase in body weight during maturation of MD rats was more pronounced in males than in females. MD anxiogenic effects were more pronounced in females, while in FST only MD males showed a marked increase in swimming activity followed by decreased immobility.
T2  - Archives of biological sciences
T1  - Maternal Deprivation of Rat Pups Reduces Body Weight and Alters Behavior in Adulthood in a Gender-Specific Manner
VL  - 67
IS  - 1
SP  - 131
EP  - 138
DO  - 10.2298/ABS141002015D
ER  - 
@article{
author = "Đorđević, Jelena D. and Mitić, Miloš and Lukić, Iva and Adžić, Miroslav",
year = "2015",
abstract = "The early postnatal environment is critical for its capacity to influence adult behavior, and is associated with traits of altered physiological and neurobiological function and long-term predisposition to depression. Here we describe the delayed effects of maternal deprivation (MD) in male and female Wistar pups on their physical development and behavior in adulthood in tasks designed to explore depressive-like (forced swimming test, FST), and anxiety-like behaviors (elevated plus maze, EPM). We observed that MD led to reduced body weight in adulthood, anxiety-like traits in the EPM test and increased activity in the phases of the FST. Particularly, a consistent sexual dimorphism was observed in the responses to MD. A lower increase in body weight during maturation of MD rats was more pronounced in males than in females. MD anxiogenic effects were more pronounced in females, while in FST only MD males showed a marked increase in swimming activity followed by decreased immobility.",
journal = "Archives of biological sciences",
title = "Maternal Deprivation of Rat Pups Reduces Body Weight and Alters Behavior in Adulthood in a Gender-Specific Manner",
volume = "67",
number = "1",
pages = "131-138",
doi = "10.2298/ABS141002015D"
}
Đorđević, J. D., Mitić, M., Lukić, I.,& Adžić, M.. (2015). Maternal Deprivation of Rat Pups Reduces Body Weight and Alters Behavior in Adulthood in a Gender-Specific Manner. in Archives of biological sciences, 67(1), 131-138.
https://doi.org/10.2298/ABS141002015D
Đorđević JD, Mitić M, Lukić I, Adžić M. Maternal Deprivation of Rat Pups Reduces Body Weight and Alters Behavior in Adulthood in a Gender-Specific Manner. in Archives of biological sciences. 2015;67(1):131-138.
doi:10.2298/ABS141002015D .
Đorđević, Jelena D., Mitić, Miloš, Lukić, Iva, Adžić, Miroslav, "Maternal Deprivation of Rat Pups Reduces Body Weight and Alters Behavior in Adulthood in a Gender-Specific Manner" in Archives of biological sciences, 67, no. 1 (2015):131-138,
https://doi.org/10.2298/ABS141002015D . .
1
1
1

Fluoxetine Signature on Hippocampal MAPK Signalling in Sex-Dependent Manner

Mitić, Miloš; Lukić, Iva; Božović, Natalija; Đorđević, Jelena D.; Adžić, Miroslav

(2015)

TY  - JOUR
AU  - Mitić, Miloš
AU  - Lukić, Iva
AU  - Božović, Natalija
AU  - Đorđević, Jelena D.
AU  - Adžić, Miroslav
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/367
AB  - A growing body of evidence indicates that mitogen-activated protein kinase (MAPK) participates in various stress-induced responses and is considered to be one of the pathophysiological mechanisms in depression. Surprisingly, the effect of antidepressants on MAPKs is almost unexplored, particularly from the perspective of sexes. The present study investigates the cytoplasm-nuclear distribution of MAPK family, c-Jun N-terminal kinases (JNKs) 1, 2 and 3; extracellular signal-regulated kinases (ERKs) 1 and 2; and p38 kinases, as well as their phosphoisoforms in the hippocampus of chronically stressed female and male rats and upon chronic fluoxetine treatment. Additionally, we analysed crosstalk between MAPK signalling and depressive-like behaviour which correlated with brain-derived neurotrophic factor (BDNF) expression. Our results emphasize a gender-specific and compartment-dependent response of MAPKs to stress and fluoxetine. In females, stress decreased pp38 and pJNK and induced cytosolic retention of pERKs which reduced all nuclear pMAPKs. These changes correlated with altered BDNF expression and behaviour. Similarly, in males, stress decreased pp38 but promoted nuclear translocation of pJNKs and pERKs. These stress alterations of pMAPKs in males were not associated with BDNF expression and depressive-like behaviour. Fluoxetine treatment in stressed females upregulated whole pMAPK signalling particularly those in nucleus which was followed with BDNF expression and normalization of behaviour. In stressed males, fluoxetine affected only cytosolic pJNKs, while nuclear pMAPK signalling and BDNF expression were unaffected even though fluoxetine normalized behaviour. Overall, our results suggest existence of gender-specific mechanism of fluoxetine on nuclear pMAPK/BDNF signalling and depressive-like behaviour and reinforce the antidepressant dogma that females and males respond differently to certain antidepressants.
T2  - Journal of Molecular Neuroscience
T1  - Fluoxetine Signature on Hippocampal MAPK Signalling in Sex-Dependent Manner
VL  - 55
IS  - 2
SP  - 335
EP  - 346
DO  - 10.1007/s12031-014-0328-1
ER  - 
@article{
author = "Mitić, Miloš and Lukić, Iva and Božović, Natalija and Đorđević, Jelena D. and Adžić, Miroslav",
year = "2015",
abstract = "A growing body of evidence indicates that mitogen-activated protein kinase (MAPK) participates in various stress-induced responses and is considered to be one of the pathophysiological mechanisms in depression. Surprisingly, the effect of antidepressants on MAPKs is almost unexplored, particularly from the perspective of sexes. The present study investigates the cytoplasm-nuclear distribution of MAPK family, c-Jun N-terminal kinases (JNKs) 1, 2 and 3; extracellular signal-regulated kinases (ERKs) 1 and 2; and p38 kinases, as well as their phosphoisoforms in the hippocampus of chronically stressed female and male rats and upon chronic fluoxetine treatment. Additionally, we analysed crosstalk between MAPK signalling and depressive-like behaviour which correlated with brain-derived neurotrophic factor (BDNF) expression. Our results emphasize a gender-specific and compartment-dependent response of MAPKs to stress and fluoxetine. In females, stress decreased pp38 and pJNK and induced cytosolic retention of pERKs which reduced all nuclear pMAPKs. These changes correlated with altered BDNF expression and behaviour. Similarly, in males, stress decreased pp38 but promoted nuclear translocation of pJNKs and pERKs. These stress alterations of pMAPKs in males were not associated with BDNF expression and depressive-like behaviour. Fluoxetine treatment in stressed females upregulated whole pMAPK signalling particularly those in nucleus which was followed with BDNF expression and normalization of behaviour. In stressed males, fluoxetine affected only cytosolic pJNKs, while nuclear pMAPK signalling and BDNF expression were unaffected even though fluoxetine normalized behaviour. Overall, our results suggest existence of gender-specific mechanism of fluoxetine on nuclear pMAPK/BDNF signalling and depressive-like behaviour and reinforce the antidepressant dogma that females and males respond differently to certain antidepressants.",
journal = "Journal of Molecular Neuroscience",
title = "Fluoxetine Signature on Hippocampal MAPK Signalling in Sex-Dependent Manner",
volume = "55",
number = "2",
pages = "335-346",
doi = "10.1007/s12031-014-0328-1"
}
Mitić, M., Lukić, I., Božović, N., Đorđević, J. D.,& Adžić, M.. (2015). Fluoxetine Signature on Hippocampal MAPK Signalling in Sex-Dependent Manner. in Journal of Molecular Neuroscience, 55(2), 335-346.
https://doi.org/10.1007/s12031-014-0328-1
Mitić M, Lukić I, Božović N, Đorđević JD, Adžić M. Fluoxetine Signature on Hippocampal MAPK Signalling in Sex-Dependent Manner. in Journal of Molecular Neuroscience. 2015;55(2):335-346.
doi:10.1007/s12031-014-0328-1 .
Mitić, Miloš, Lukić, Iva, Božović, Natalija, Đorđević, Jelena D., Adžić, Miroslav, "Fluoxetine Signature on Hippocampal MAPK Signalling in Sex-Dependent Manner" in Journal of Molecular Neuroscience, 55, no. 2 (2015):335-346,
https://doi.org/10.1007/s12031-014-0328-1 . .
1
7
5
8

The role of glucocorticoid receptor phosphorylation in the model of negative affective states

Jovičić, Milica; Maric, Nadja P.; Soldatovic, Ivan; Lukić, Iva; Andrić, Sanja; Mihaljevic, Marina; Pavlović, Zorana; Mitić, Miloš; Adžić, Miroslav

(2015)

TY  - JOUR
AU  - Jovičić, Milica
AU  - Maric, Nadja P.
AU  - Soldatovic, Ivan
AU  - Lukić, Iva
AU  - Andrić, Sanja
AU  - Mihaljevic, Marina
AU  - Pavlović, Zorana
AU  - Mitić, Miloš
AU  - Adžić, Miroslav
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/707
AB  - Objectives. To develop a structural equation model of negative affectivity (NA) that involves interaction of glucocorticoid receptor (GR) signaling, personality dimensions and recent stressful life events. Methods. Seventy participants -35 diagnosed with major depression and 35 healthy controls, were enrolled in the study. Morning plasma cortisol levels were determined by chemiluminescent immunometric assays. Molecular parameters (total nuclear and cytoplasmatic GR, nuclear GR phosphorylated at serine 211 (pGR-211) and at serine 226 (pGR-226) and cytoplasmic FKBP51) were analysed from peripheral blood lymphocytes by Western blot. NA, personality dimensions and stressful life events were assessed by self-report instruments. Results. GR signalling parameters had direct independent effect on measures of NA, with pGR-226 levels showing the strongest correlation, followed by FKBP51 and pGR-211 levels. Neuroticism and extraversion also demonstrated strong independent effect on NA, while recent stressful events did not predict NA directly, but demonstrated a significant effect on personality dimensions. Cortisol, total nuclear GR and total cytoplasmatic GR levels were excluded from the model due to non-significant correlations with NA. Conclusions. Negative affectivity is a transdiagnostic factor in vulnerability to affective disorders and possible therapeutic target. Molecular signature of negative affectivity should incorporate GR phosphorylation with other known biological underpinnings.
T2  - World Journal of Biological Psychiatry
T1  - The role of glucocorticoid receptor phosphorylation in the model of negative affective states
VL  - 16
IS  - 5
SP  - 301
EP  - 311
DO  - 10.3109/15622975.2014.1000375
ER  - 
@article{
author = "Jovičić, Milica and Maric, Nadja P. and Soldatovic, Ivan and Lukić, Iva and Andrić, Sanja and Mihaljevic, Marina and Pavlović, Zorana and Mitić, Miloš and Adžić, Miroslav",
year = "2015",
abstract = "Objectives. To develop a structural equation model of negative affectivity (NA) that involves interaction of glucocorticoid receptor (GR) signaling, personality dimensions and recent stressful life events. Methods. Seventy participants -35 diagnosed with major depression and 35 healthy controls, were enrolled in the study. Morning plasma cortisol levels were determined by chemiluminescent immunometric assays. Molecular parameters (total nuclear and cytoplasmatic GR, nuclear GR phosphorylated at serine 211 (pGR-211) and at serine 226 (pGR-226) and cytoplasmic FKBP51) were analysed from peripheral blood lymphocytes by Western blot. NA, personality dimensions and stressful life events were assessed by self-report instruments. Results. GR signalling parameters had direct independent effect on measures of NA, with pGR-226 levels showing the strongest correlation, followed by FKBP51 and pGR-211 levels. Neuroticism and extraversion also demonstrated strong independent effect on NA, while recent stressful events did not predict NA directly, but demonstrated a significant effect on personality dimensions. Cortisol, total nuclear GR and total cytoplasmatic GR levels were excluded from the model due to non-significant correlations with NA. Conclusions. Negative affectivity is a transdiagnostic factor in vulnerability to affective disorders and possible therapeutic target. Molecular signature of negative affectivity should incorporate GR phosphorylation with other known biological underpinnings.",
journal = "World Journal of Biological Psychiatry",
title = "The role of glucocorticoid receptor phosphorylation in the model of negative affective states",
volume = "16",
number = "5",
pages = "301-311",
doi = "10.3109/15622975.2014.1000375"
}
Jovičić, M., Maric, N. P., Soldatovic, I., Lukić, I., Andrić, S., Mihaljevic, M., Pavlović, Z., Mitić, M.,& Adžić, M.. (2015). The role of glucocorticoid receptor phosphorylation in the model of negative affective states. in World Journal of Biological Psychiatry, 16(5), 301-311.
https://doi.org/10.3109/15622975.2014.1000375
Jovičić M, Maric NP, Soldatovic I, Lukić I, Andrić S, Mihaljevic M, Pavlović Z, Mitić M, Adžić M. The role of glucocorticoid receptor phosphorylation in the model of negative affective states. in World Journal of Biological Psychiatry. 2015;16(5):301-311.
doi:10.3109/15622975.2014.1000375 .
Jovičić, Milica, Maric, Nadja P., Soldatovic, Ivan, Lukić, Iva, Andrić, Sanja, Mihaljevic, Marina, Pavlović, Zorana, Mitić, Miloš, Adžić, Miroslav, "The role of glucocorticoid receptor phosphorylation in the model of negative affective states" in World Journal of Biological Psychiatry, 16, no. 5 (2015):301-311,
https://doi.org/10.3109/15622975.2014.1000375 . .
2
9
5
5

Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients

Lukić, Iva; Mitić, Miloš; Soldatovic, Ivan; Jovičić, Milica; Maric, Nadja; Radulovic, Jelena; Adžić, Miroslav

(2015)

TY  - JOUR
AU  - Lukić, Iva
AU  - Mitić, Miloš
AU  - Soldatovic, Ivan
AU  - Jovičić, Milica
AU  - Maric, Nadja
AU  - Radulovic, Jelena
AU  - Adžić, Miroslav
PY  - 2015
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/445
AB  - We have previously shown that patients with the major depressive disorder (MDD) exhibited elevated phosphorylation of the lymphocyte glucocorticoid receptor (GR) at serine 226 (S226). Here, we further analyse potential alterations of GR signalization in lymphocytes of MDD patients, i.e. the cytoplasmic/nuclear distribution of GR, levels of FK506-binding protein 5 (FKBP5) and glucocorticoid-induced leucine zipper (GILZ). The FKBP5 acts as an important regulator of GR activation, by decreasing ligand binding and impeding translocation of the receptor to the nucleus, while GILZ mediates glucocorticoid anti-inflammatory effects. Our result showed that the depressed patients had significantly higher GR levels in the cytoplasm compared to controls, which was accompanied by higher FKBP5 levels. Linear regression model demonstrated significantly higher correlation between FKBP5 and cytoplasmic GR than the presence of MDD itself or phosphorylation of nuclear GR at S226. There were no differences in the levels of GILZ isoforms. Therefore, the results suggest that accumulation of the GR in cytoplasm is related to the elevation of FKBP5, adding one more step in understanding altered GR signalling in lymphocytes, and potentially brain tissue, of MDD patients.
T2  - Journal of Molecular Neuroscience
T1  - Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients
VL  - 55
IS  - 4
SP  - 951
EP  - 958
DO  - 10.1007/s12031-014-0451-z
ER  - 
@article{
author = "Lukić, Iva and Mitić, Miloš and Soldatovic, Ivan and Jovičić, Milica and Maric, Nadja and Radulovic, Jelena and Adžić, Miroslav",
year = "2015",
abstract = "We have previously shown that patients with the major depressive disorder (MDD) exhibited elevated phosphorylation of the lymphocyte glucocorticoid receptor (GR) at serine 226 (S226). Here, we further analyse potential alterations of GR signalization in lymphocytes of MDD patients, i.e. the cytoplasmic/nuclear distribution of GR, levels of FK506-binding protein 5 (FKBP5) and glucocorticoid-induced leucine zipper (GILZ). The FKBP5 acts as an important regulator of GR activation, by decreasing ligand binding and impeding translocation of the receptor to the nucleus, while GILZ mediates glucocorticoid anti-inflammatory effects. Our result showed that the depressed patients had significantly higher GR levels in the cytoplasm compared to controls, which was accompanied by higher FKBP5 levels. Linear regression model demonstrated significantly higher correlation between FKBP5 and cytoplasmic GR than the presence of MDD itself or phosphorylation of nuclear GR at S226. There were no differences in the levels of GILZ isoforms. Therefore, the results suggest that accumulation of the GR in cytoplasm is related to the elevation of FKBP5, adding one more step in understanding altered GR signalling in lymphocytes, and potentially brain tissue, of MDD patients.",
journal = "Journal of Molecular Neuroscience",
title = "Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients",
volume = "55",
number = "4",
pages = "951-958",
doi = "10.1007/s12031-014-0451-z"
}
Lukić, I., Mitić, M., Soldatovic, I., Jovičić, M., Maric, N., Radulovic, J.,& Adžić, M.. (2015). Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients. in Journal of Molecular Neuroscience, 55(4), 951-958.
https://doi.org/10.1007/s12031-014-0451-z
Lukić I, Mitić M, Soldatovic I, Jovičić M, Maric N, Radulovic J, Adžić M. Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients. in Journal of Molecular Neuroscience. 2015;55(4):951-958.
doi:10.1007/s12031-014-0451-z .
Lukić, Iva, Mitić, Miloš, Soldatovic, Ivan, Jovičić, Milica, Maric, Nadja, Radulovic, Jelena, Adžić, Miroslav, "Accumulation of Cytoplasmic Glucocorticoid Receptor Is Related to Elevation of FKBP5 in Lymphocytes of Depressed Patients" in Journal of Molecular Neuroscience, 55, no. 4 (2015):951-958,
https://doi.org/10.1007/s12031-014-0451-z . .
1
18
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17

Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients

Lukić, Iva; Mitić, Miloš; Đorđević, Jelena D.; Tatalović, Nikola R.; Božović, Natalija; Soldatovic, Ivan; Mihaljevic, Marina; Pavlović, Zorana; Radoičić, Marija B.; Maric, Nadja P.; Adžić, Miroslav

(2014)

TY  - JOUR
AU  - Lukić, Iva
AU  - Mitić, Miloš
AU  - Đorđević, Jelena D.
AU  - Tatalović, Nikola R.
AU  - Božović, Natalija
AU  - Soldatovic, Ivan
AU  - Mihaljevic, Marina
AU  - Pavlović, Zorana
AU  - Radoičić, Marija B.
AU  - Maric, Nadja P.
AU  - Adžić, Miroslav
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/148
AB  - Background: Oxidative stress is reliably observed in major depressive disorder (MDD). However, molecular data on the principal cellular redox-sensitive transcriptional factors and the levels of their downstream-regulated antioxidant enzymes in MDD are scarce. Methods: In the peripheral blood mononuclear cells (PBMC) of subjects with a current episode of MDD (n = 30) and healthy controls (n = 35), we investigated alterations in the levels of redox-sensing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein, its inhibitor Keap1, and nuclear factor-kappa B (NF-kappa B), along with their cognate downstream effectors, the antioxidant enzymes (AOEs): manganese and copper zinc superoxide dismutase (MnSOD and CuZnSOD, respectively), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR). Results: MDD subjects exhibited higher levels of Nrf2 and its regulator Keap1, as well as NF-kappa B in the cytoplasm of PBMC compared to controls. This state was further reflected by increased levels of MnSOD, CuZnSOD and CAT proteins and by the lack of correlation between MnSOD and CAT, which could indicate impaired oxidative detoxification capacity in MDD patients. Moreover, increased levels of MnSOD, CuZnSOD and CAT in MDD patients positively correlated with levels of Nrf2, while increased levels of SODs were also positively related to NF-kappa B. There were no differences regarding the levels of GPx and GLR proteins, but the ratio of GLR/GPx was reduced, suggesting diminished capacity of GPx in antioxidative defence in PBMC of MDD subjects. Conclusion: These data provide evidence that MDD is characterized by up-regulation of redox-sensitive transcriptional factors (Nrf2 and NF-kappa B) and AOEs (MnSOD, CuZnSOD and CAT), indicating pro-oxidative state in the PBMC of MDD patients. (C) 2014 S. Karger AG, Basel
T2  - Neuropsychobiology
T1  - Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients
VL  - 70
IS  - 1
SP  - 1
EP  - 9
DO  - 10.1159/000362841
ER  - 
@article{
author = "Lukić, Iva and Mitić, Miloš and Đorđević, Jelena D. and Tatalović, Nikola R. and Božović, Natalija and Soldatovic, Ivan and Mihaljevic, Marina and Pavlović, Zorana and Radoičić, Marija B. and Maric, Nadja P. and Adžić, Miroslav",
year = "2014",
abstract = "Background: Oxidative stress is reliably observed in major depressive disorder (MDD). However, molecular data on the principal cellular redox-sensitive transcriptional factors and the levels of their downstream-regulated antioxidant enzymes in MDD are scarce. Methods: In the peripheral blood mononuclear cells (PBMC) of subjects with a current episode of MDD (n = 30) and healthy controls (n = 35), we investigated alterations in the levels of redox-sensing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein, its inhibitor Keap1, and nuclear factor-kappa B (NF-kappa B), along with their cognate downstream effectors, the antioxidant enzymes (AOEs): manganese and copper zinc superoxide dismutase (MnSOD and CuZnSOD, respectively), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR). Results: MDD subjects exhibited higher levels of Nrf2 and its regulator Keap1, as well as NF-kappa B in the cytoplasm of PBMC compared to controls. This state was further reflected by increased levels of MnSOD, CuZnSOD and CAT proteins and by the lack of correlation between MnSOD and CAT, which could indicate impaired oxidative detoxification capacity in MDD patients. Moreover, increased levels of MnSOD, CuZnSOD and CAT in MDD patients positively correlated with levels of Nrf2, while increased levels of SODs were also positively related to NF-kappa B. There were no differences regarding the levels of GPx and GLR proteins, but the ratio of GLR/GPx was reduced, suggesting diminished capacity of GPx in antioxidative defence in PBMC of MDD subjects. Conclusion: These data provide evidence that MDD is characterized by up-regulation of redox-sensitive transcriptional factors (Nrf2 and NF-kappa B) and AOEs (MnSOD, CuZnSOD and CAT), indicating pro-oxidative state in the PBMC of MDD patients. (C) 2014 S. Karger AG, Basel",
journal = "Neuropsychobiology",
title = "Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients",
volume = "70",
number = "1",
pages = "1-9",
doi = "10.1159/000362841"
}
Lukić, I., Mitić, M., Đorđević, J. D., Tatalović, N. R., Božović, N., Soldatovic, I., Mihaljevic, M., Pavlović, Z., Radoičić, M. B., Maric, N. P.,& Adžić, M.. (2014). Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients. in Neuropsychobiology, 70(1), 1-9.
https://doi.org/10.1159/000362841
Lukić I, Mitić M, Đorđević JD, Tatalović NR, Božović N, Soldatovic I, Mihaljevic M, Pavlović Z, Radoičić MB, Maric NP, Adžić M. Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients. in Neuropsychobiology. 2014;70(1):1-9.
doi:10.1159/000362841 .
Lukić, Iva, Mitić, Miloš, Đorđević, Jelena D., Tatalović, Nikola R., Božović, Natalija, Soldatovic, Ivan, Mihaljevic, Marina, Pavlović, Zorana, Radoičić, Marija B., Maric, Nadja P., Adžić, Miroslav, "Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients" in Neuropsychobiology, 70, no. 1 (2014):1-9,
https://doi.org/10.1159/000362841 . .
23
22
22

Association of female gonadal hormones and immunity in depression

Mitić, Miloš; Lukić, Iva; Đorđević, Jelena D.; Adžić, Miroslav

(Society of Physical Chemists of Serbia, 2014)

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

Fluoxetine normalized nuclear phospho erk1/2 signaling in stressed females

Mitić, Miloš; Lukić, Iva; Božović, N.; Đorđević, Jelena D.; Adžić, Miroslav

(Society of Physical Chemists of Serbia, 2014)

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