Franić, Dušanka

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orcid::0000-0002-9702-2120
  • Franić, Dušanka (7)
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Author's Bibliography

The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls

Mihaljević, Marina; Franić, Dušanka; Soldatović, Ivan A.; Lukić, Iva; Andrić-Petrović, Sanja; Mirjanić, Tijana; Stanković, Biljana; Žukić, Branka; Željić, Katarina; Gašić, Vladimir; Novaković, Ivana; Pavlović, Sonja; Adžić, Miroslav; Marić, Nađa P.

(2021)

TY  - JOUR
AU  - Mihaljević, Marina
AU  - Franić, Dušanka
AU  - Soldatović, Ivan A.
AU  - Lukić, Iva
AU  - Andrić-Petrović, Sanja
AU  - Mirjanić, Tijana
AU  - Stanković, Biljana
AU  - Žukić, Branka
AU  - Željić, Katarina
AU  - Gašić, Vladimir
AU  - Novaković, Ivana
AU  - Pavlović, Sonja
AU  - Adžić, Miroslav
AU  - Marić, Nađa P.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9748
AB  - Hypothalamic–pituitary–adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation. © 2021 Elsevier Ltd
T2  - Psychoneuroendocrinology
T1  - The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls
VL  - 128
SP  - 105205
DO  - 10.1016/j.psyneuen.2021.105205
ER  - 
@article{
author = "Mihaljević, Marina and Franić, Dušanka and Soldatović, Ivan A. and Lukić, Iva and Andrić-Petrović, Sanja and Mirjanić, Tijana and Stanković, Biljana and Žukić, Branka and Željić, Katarina and Gašić, Vladimir and Novaković, Ivana and Pavlović, Sonja and Adžić, Miroslav and Marić, Nađa P.",
year = "2021",
abstract = "Hypothalamic–pituitary–adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation. © 2021 Elsevier Ltd",
journal = "Psychoneuroendocrinology",
title = "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls",
volume = "128",
pages = "105205",
doi = "10.1016/j.psyneuen.2021.105205"
}
Mihaljević, M., Franić, D., Soldatović, I. A., Lukić, I., Andrić-Petrović, S., Mirjanić, T., Stanković, B., Žukić, B., Željić, K., Gašić, V., Novaković, I., Pavlović, S., Adžić, M.,& Marić, N. P.. (2021). The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology, 128, 105205.
https://doi.org/10.1016/j.psyneuen.2021.105205
Mihaljević M, Franić D, Soldatović IA, Lukić I, Andrić-Petrović S, Mirjanić T, Stanković B, Žukić B, Željić K, Gašić V, Novaković I, Pavlović S, Adžić M, Marić NP. The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology. 2021;128:105205.
doi:10.1016/j.psyneuen.2021.105205 .
Mihaljević, Marina, Franić, Dušanka, Soldatović, Ivan A., Lukić, Iva, Andrić-Petrović, Sanja, Mirjanić, Tijana, Stanković, Biljana, Žukić, Branka, Željić, Katarina, Gašić, Vladimir, Novaković, Ivana, Pavlović, Sonja, Adžić, Miroslav, Marić, Nađa P., "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls" in Psychoneuroendocrinology, 128 (2021):105205,
https://doi.org/10.1016/j.psyneuen.2021.105205 . .
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7
2
5

Allele-Specific and Trauma-Related Epigenetic Changes in the Fkbp5 Gene: Differences Between Psychotic Patients and Healthy Controls

Mihaljević, Marina; Franić, Dušanka; Soldatovic, Ivan; Andrić, Sanja; Mirjanic, Tijana; Novaković, Ivana; Adžić, Miroslav; Marić, Nađa

(2017)

TY  - CONF
AU  - Mihaljević, Marina
AU  - Franić, Dušanka
AU  - Soldatovic, Ivan
AU  - Andrić, Sanja
AU  - Mirjanic, Tijana
AU  - Novaković, Ivana
AU  - Adžić, Miroslav
AU  - Marić, Nađa
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7157
C3  - Schizophrenia Bulletin
T1  - Allele-Specific and Trauma-Related Epigenetic Changes in the Fkbp5 Gene: Differences Between Psychotic Patients and Healthy Controls
VL  - 43
SP  - S195
EP  - S195
UR  - https://hdl.handle.net/21.15107/rcub_vinar_7157
ER  - 
@conference{
author = "Mihaljević, Marina and Franić, Dušanka and Soldatovic, Ivan and Andrić, Sanja and Mirjanic, Tijana and Novaković, Ivana and Adžić, Miroslav and Marić, Nađa",
year = "2017",
journal = "Schizophrenia Bulletin",
title = "Allele-Specific and Trauma-Related Epigenetic Changes in the Fkbp5 Gene: Differences Between Psychotic Patients and Healthy Controls",
volume = "43",
pages = "S195-S195",
url = "https://hdl.handle.net/21.15107/rcub_vinar_7157"
}
Mihaljević, M., Franić, D., Soldatovic, I., Andrić, S., Mirjanic, T., Novaković, I., Adžić, M.,& Marić, N.. (2017). Allele-Specific and Trauma-Related Epigenetic Changes in the Fkbp5 Gene: Differences Between Psychotic Patients and Healthy Controls. in Schizophrenia Bulletin, 43, S195-S195.
https://hdl.handle.net/21.15107/rcub_vinar_7157
Mihaljević M, Franić D, Soldatovic I, Andrić S, Mirjanic T, Novaković I, Adžić M, Marić N. Allele-Specific and Trauma-Related Epigenetic Changes in the Fkbp5 Gene: Differences Between Psychotic Patients and Healthy Controls. in Schizophrenia Bulletin. 2017;43:S195-S195.
https://hdl.handle.net/21.15107/rcub_vinar_7157 .
Mihaljević, Marina, Franić, Dušanka, Soldatovic, Ivan, Andrić, Sanja, Mirjanic, Tijana, Novaković, Ivana, Adžić, Miroslav, Marić, Nađa, "Allele-Specific and Trauma-Related Epigenetic Changes in the Fkbp5 Gene: Differences Between Psychotic Patients and Healthy Controls" in Schizophrenia Bulletin, 43 (2017):S195-S195,
https://hdl.handle.net/21.15107/rcub_vinar_7157 .

The Signature of Trauma in Psychosis: a Preliminary Genetic and Epigenetic Analyses of Fk506-Binding Protein 5 Regulation

Marić, Nađa; Mihaljević, Marina; Franić, Dušanka; Soldatovic, Ivan; Andrić, Sanja; Lukić, Iva; Mirjanic, Tijana; Stankovic, Biljana; Zukic, Branka; Dobricic, Valerija; Novaković, Ivana; Pavlović, Sonja; Adžić, Miroslav

(2017)

TY  - CONF
AU  - Marić, Nađa
AU  - Mihaljević, Marina
AU  - Franić, Dušanka
AU  - Soldatovic, Ivan
AU  - Andrić, Sanja
AU  - Lukić, Iva
AU  - Mirjanic, Tijana
AU  - Stankovic, Biljana
AU  - Zukic, Branka
AU  - Dobricic, Valerija
AU  - Novaković, Ivana
AU  - Pavlović, Sonja
AU  - Adžić, Miroslav
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7156
C3  - Schizophrenia Bulletin
T1  - The Signature of Trauma in Psychosis: a Preliminary Genetic and Epigenetic Analyses of Fk506-Binding Protein 5 Regulation
VL  - 43
SP  - S66
EP  - S66
UR  - https://hdl.handle.net/21.15107/rcub_vinar_7156
ER  - 
@conference{
author = "Marić, Nađa and Mihaljević, Marina and Franić, Dušanka and Soldatovic, Ivan and Andrić, Sanja and Lukić, Iva and Mirjanic, Tijana and Stankovic, Biljana and Zukic, Branka and Dobricic, Valerija and Novaković, Ivana and Pavlović, Sonja and Adžić, Miroslav",
year = "2017",
journal = "Schizophrenia Bulletin",
title = "The Signature of Trauma in Psychosis: a Preliminary Genetic and Epigenetic Analyses of Fk506-Binding Protein 5 Regulation",
volume = "43",
pages = "S66-S66",
url = "https://hdl.handle.net/21.15107/rcub_vinar_7156"
}
Marić, N., Mihaljević, M., Franić, D., Soldatovic, I., Andrić, S., Lukić, I., Mirjanic, T., Stankovic, B., Zukic, B., Dobricic, V., Novaković, I., Pavlović, S.,& Adžić, M.. (2017). The Signature of Trauma in Psychosis: a Preliminary Genetic and Epigenetic Analyses of Fk506-Binding Protein 5 Regulation. in Schizophrenia Bulletin, 43, S66-S66.
https://hdl.handle.net/21.15107/rcub_vinar_7156
Marić N, Mihaljević M, Franić D, Soldatovic I, Andrić S, Lukić I, Mirjanic T, Stankovic B, Zukic B, Dobricic V, Novaković I, Pavlović S, Adžić M. The Signature of Trauma in Psychosis: a Preliminary Genetic and Epigenetic Analyses of Fk506-Binding Protein 5 Regulation. in Schizophrenia Bulletin. 2017;43:S66-S66.
https://hdl.handle.net/21.15107/rcub_vinar_7156 .
Marić, Nađa, Mihaljević, Marina, Franić, Dušanka, Soldatovic, Ivan, Andrić, Sanja, Lukić, Iva, Mirjanic, Tijana, Stankovic, Biljana, Zukic, Branka, Dobricic, Valerija, Novaković, Ivana, Pavlović, Sonja, Adžić, Miroslav, "The Signature of Trauma in Psychosis: a Preliminary Genetic and Epigenetic Analyses of Fk506-Binding Protein 5 Regulation" in Schizophrenia Bulletin, 43 (2017):S66-S66,
https://hdl.handle.net/21.15107/rcub_vinar_7156 .

Fkbp5 Epigenetic Changes in Schizophrenia: Similarity to Stress-Related Conditions

Mihaljević, Marina; Franić, Dušanka; Soldatovic, Ivan; Andrić, Sanja; Mirjanic, Tijana; Novaković, Ivana; Adžić, Miroslav; Nadja, Maric

(2017)

TY  - CONF
AU  - Mihaljević, Marina
AU  - Franić, Dušanka
AU  - Soldatovic, Ivan
AU  - Andrić, Sanja
AU  - Mirjanic, Tijana
AU  - Novaković, Ivana
AU  - Adžić, Miroslav
AU  - Nadja, Maric
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7185
C3  - European Neuropsychopharmacology
T1  - Fkbp5 Epigenetic Changes in Schizophrenia: Similarity to Stress-Related Conditions
VL  - 27
SP  - S461
EP  - S462
DO  - 10.1016/j.euroneuro.2016.09.535
ER  - 
@conference{
author = "Mihaljević, Marina and Franić, Dušanka and Soldatovic, Ivan and Andrić, Sanja and Mirjanic, Tijana and Novaković, Ivana and Adžić, Miroslav and Nadja, Maric",
year = "2017",
journal = "European Neuropsychopharmacology",
title = "Fkbp5 Epigenetic Changes in Schizophrenia: Similarity to Stress-Related Conditions",
volume = "27",
pages = "S461-S462",
doi = "10.1016/j.euroneuro.2016.09.535"
}
Mihaljević, M., Franić, D., Soldatovic, I., Andrić, S., Mirjanic, T., Novaković, I., Adžić, M.,& Nadja, M.. (2017). Fkbp5 Epigenetic Changes in Schizophrenia: Similarity to Stress-Related Conditions. in European Neuropsychopharmacology, 27, S461-S462.
https://doi.org/10.1016/j.euroneuro.2016.09.535
Mihaljević M, Franić D, Soldatovic I, Andrić S, Mirjanic T, Novaković I, Adžić M, Nadja M. Fkbp5 Epigenetic Changes in Schizophrenia: Similarity to Stress-Related Conditions. in European Neuropsychopharmacology. 2017;27:S461-S462.
doi:10.1016/j.euroneuro.2016.09.535 .
Mihaljević, Marina, Franić, Dušanka, Soldatovic, Ivan, Andrić, Sanja, Mirjanic, Tijana, Novaković, Ivana, Adžić, Miroslav, Nadja, Maric, "Fkbp5 Epigenetic Changes in Schizophrenia: Similarity to Stress-Related Conditions" in European Neuropsychopharmacology, 27 (2017):S461-S462,
https://doi.org/10.1016/j.euroneuro.2016.09.535 . .

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
9

Epigenetic signature of early trauma: differences in the FKBP5 DNA methylation levels among psychotic patients, their healthy siblings and controls

Mihaljevic, M.; Franić, Dušanka; Soldatovic, I.; Andric, S.; Stankovic, B.; Zukic, B.; Pavlović, Suncan; Adžić, Miroslav; Maric, N.

(2017)

TY  - CONF
AU  - Mihaljevic, M.
AU  - Franić, Dušanka
AU  - Soldatovic, I.
AU  - Andric, S.
AU  - Stankovic, B.
AU  - Zukic, B.
AU  - Pavlović, Suncan
AU  - Adžić, Miroslav
AU  - Maric, N.
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7186
C3  - European Neuropsychopharmacology
T1  - Epigenetic signature of early trauma: differences in the FKBP5 DNA methylation levels among psychotic patients, their healthy siblings and controls
VL  - 27
SP  - S967
EP  - S968
UR  - https://hdl.handle.net/21.15107/rcub_vinar_7186
ER  - 
@conference{
author = "Mihaljevic, M. and Franić, Dušanka and Soldatovic, I. and Andric, S. and Stankovic, B. and Zukic, B. and Pavlović, Suncan and Adžić, Miroslav and Maric, N.",
year = "2017",
journal = "European Neuropsychopharmacology",
title = "Epigenetic signature of early trauma: differences in the FKBP5 DNA methylation levels among psychotic patients, their healthy siblings and controls",
volume = "27",
pages = "S967-S968",
url = "https://hdl.handle.net/21.15107/rcub_vinar_7186"
}
Mihaljevic, M., Franić, D., Soldatovic, I., Andric, S., Stankovic, B., Zukic, B., Pavlović, S., Adžić, M.,& Maric, N.. (2017). Epigenetic signature of early trauma: differences in the FKBP5 DNA methylation levels among psychotic patients, their healthy siblings and controls. in European Neuropsychopharmacology, 27, S967-S968.
https://hdl.handle.net/21.15107/rcub_vinar_7186
Mihaljevic M, Franić D, Soldatovic I, Andric S, Stankovic B, Zukic B, Pavlović S, Adžić M, Maric N. Epigenetic signature of early trauma: differences in the FKBP5 DNA methylation levels among psychotic patients, their healthy siblings and controls. in European Neuropsychopharmacology. 2017;27:S967-S968.
https://hdl.handle.net/21.15107/rcub_vinar_7186 .
Mihaljevic, M., Franić, Dušanka, Soldatovic, I., Andric, S., Stankovic, B., Zukic, B., Pavlović, Suncan, Adžić, Miroslav, Maric, N., "Epigenetic signature of early trauma: differences in the FKBP5 DNA methylation levels among psychotic patients, their healthy siblings and controls" in European Neuropsychopharmacology, 27 (2017):S967-S968,
https://hdl.handle.net/21.15107/rcub_vinar_7186 .

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 . .
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