Glucocorticoid receptor alpha translational isoforms as mediators of early adversities and negative emotional states
Само за регистроване кориснике
2019
Аутори
Adžić, MiroslavGlavonić, 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.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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. T...he 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.
Кључне речи:
Childhood trauma / Glucocorticoid receptor / Fear conditioning / PlasticityИзвор:
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2019, 90, 288-299Финансирање / пројекти:
- Дефинисање кластера молекулских биомаркера за побољшану дијагностику и терапију поремећаја расположења (RS-41029)
- NIH grant (R21MH098793)
Напомена:
- Free Author Manuscript available at PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383671/
DOI: 10.1016/j.pnpbp.2018.12.011
ISSN: 0278-5846
PubMed: 30580022
WoS: 000454536600029
Scopus: 2-s2.0-85058786978
Институција/група
VinčaTY - 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 . .