Prikaz osnovnih podataka o dokumentu
Glucocorticoid receptor alpha translational isoforms as mediators of early adversities and negative emotional states
dc.creator | Adžić, Miroslav | |
dc.creator | Glavonić, Emilija | |
dc.creator | Nešić, Milica J. | |
dc.creator | Milosavljević, Minja | |
dc.creator | Mihaljević, Marina | |
dc.creator | Petrović, Zorica D. | |
dc.creator | Pavlović, Zorana | |
dc.creator | Brkić, Željka | |
dc.creator | Francija, Ester | |
dc.creator | Soldatović, Ivan A. | |
dc.creator | Mitić, Miloš | |
dc.creator | Radulović, Jelena | |
dc.creator | Marić, Nađa P. | |
dc.date.accessioned | 2019-01-30T16:38:30Z | |
dc.date.available | 2019-01-30T16:38:30Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 0278-5846 | |
dc.identifier.uri | https://vinar.vin.bg.ac.rs/handle/123456789/8010 | |
dc.description.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. | en |
dc.language.iso | en | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41029/RS// | |
dc.relation | NIH grant (R21MH098793) | |
dc.rights | restrictedAccess | |
dc.source | Progress in Neuro-Psychopharmacology and Biological Psychiatry | |
dc.subject | Childhood trauma | en |
dc.subject | Glucocorticoid receptor | en |
dc.subject | Fear conditioning | en |
dc.subject | Plasticity | en |
dc.title | Glucocorticoid receptor alpha translational isoforms as mediators of early adversities and negative emotional states | en |
dc.type | article | en |
dc.rights.license | ARR | |
dcterms.abstract | Бркић, Жељка; Aджић, Мирослав; Марић, Нађа П.; Радуловић, Јелена; Петровић, Зорица; Митић, Милош; Главонић, Емилија; Нешић, Милица Ј.; Милосављевић, Миња; Михаљевић, Марина; Павловић, Зорана; Солдатовић, Иван; Франција, Естер; | |
dc.citation.volume | 90 | |
dc.citation.spage | 288 | |
dc.citation.epage | 299 | |
dc.identifier.wos | 000454536600029 | |
dc.identifier.doi | 10.1016/j.pnpbp.2018.12.011 | |
dc.citation.rank | M21 | |
dc.identifier.pmid | 30580022 | |
dc.description.other | Free Author Manuscript available at PMC: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383671/] | |
dc.type.version | publishedVersion | |
dc.identifier.scopus | 2-s2.0-85058786978 |
Dokumenti
Ovaj dokument se pojavljuje u sledećim kolekcijama
-
090 - Laboratorija za molekularnu biologiju i endokrinologiju
Department of Molecular Biology and Endocrinology -
Radovi istraživača
Researchers' publications