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dc.creatorAdžić, Miroslav
dc.creatorGlavonić, Emilija
dc.creatorNešić, Milica J.
dc.creatorMilosavljević, Minja
dc.creatorMihaljević, Marina
dc.creatorPetrović, Zorica D.
dc.creatorPavlović, Zorana
dc.creatorBrkić, Željka
dc.creatorFrancija, Ester
dc.creatorSoldatović, Ivan A.
dc.creatorMitić, Miloš
dc.creatorRadulović, Jelena
dc.creatorMarić, Nađa P.
dc.date.accessioned2019-01-30T16:38:30Z
dc.date.available2019-01-30T16:38:30Z
dc.date.issued2019
dc.identifier.issn0278-5846 (print)
dc.identifier.issn1878-4216 (electronic)
dc.identifier.urihttps://linkinghub.elsevier.com/retrieve/pii/S0278584618305670
dc.identifier.urihttp://vinar.vin.bg.ac.rs/handle/123456789/8010
dc.description.abstractChildhood 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.
dc.language.isoen
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41029/RS//
dc.relationNIH grant (R21MH098793)
dc.rightsrestrictedAccess
dc.sourceProgress in Neuro-Psychopharmacology and Biological Psychiatry
dc.subjectChildhood traumaen
dc.subjectGlucocorticoid receptoren
dc.subjectFear conditioningen
dc.subjectPlasticityen
dc.titleGlucocorticoid receptor alpha translational isoforms as mediators of early adversities and negative emotional statesen
dc.typearticleen
dc.rights.licenseARR
dcterms.abstractБркић, 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.rights.holder© 2018 Elsevier Inc
dc.citation.volume90
dc.citation.spage288
dc.citation.epage299
dc.identifier.wos000454536600029
dc.identifier.doi10.1016/j.pnpbp.2018.12.011
dc.identifier.pmid30580022
dc.type.versionpublishedVersion
dc.identifier.scopus2-s2.0-85058786978


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