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dc.contributor.authorNotaras, M
dc.contributor.authorDu, X
dc.contributor.authorGogos, J
dc.contributor.authorvan den Buuse, M
dc.contributor.authorHill, RA
dc.date.accessioned2020-12-17T03:56:11Z
dc.date.available2020-12-17T03:56:11Z
dc.date.issued2017-09-19
dc.identifierpii: tp2017205
dc.identifier.citationNotaras, M., Du, X., Gogos, J., van den Buuse, M. & Hill, R. A. (2017). The BDNF Val66Met polymorphism regulates glucocorticoid-induced corticohippocampal remodeling and behavioral despair. TRANSLATIONAL PSYCHIATRY, 7 (9), https://doi.org/10.1038/tp.2017.205.
dc.identifier.issn2158-3188
dc.identifier.urihttp://hdl.handle.net/11343/255095
dc.description.abstractThe BDNF Val66Met polymorphism has been associated with sensitivity to stress and affective disorders. We therefore sought to model the inter-causality of these relationships under controlled laboratory conditions. We subjected humanized BDNF Val66Met (hBDNFVal66Met) transgenic mice to a history of stress, modeled by chronic late-adolescent corticosterone (CORT) exposure, before evaluating affective-related behavior using the forced-swim test (FST) in adulthood. While hBDNFMet/Met mice had a depression-like phenotype in the FST irrespective of CORT, hBDNFVal/Val wildtype mice had a resilient phenotype but developed an equally robust depressive-like phenotype following CORT. A range of stress-sensitive molecules were studied across the corticohippocampal axis, and where genotype differences occurred following CORT they tended to inversely coincide with the behavior of the hBDNFVal/Val group. Notably, tyrosine hydroxylase was markedly down-regulated in the mPFC of hBDNFVal/Val mice as a result of CORT treatment, which mimicked expression levels of hBDNFMet/Met mice and the FST behavior of both groups. The expression of calretinin, PSD-95, and truncated TrkB were also concomitantly reduced in the mPFC of hBDNFVal/Val mice by CORT. This work establishes BDNFVal66Met genotype as a regulator of behavioral despair, and identifies new biological targets of BDNF genetic variation relevant to stress-inducible disorders such as depression.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleThe BDNF Val66Met polymorphism regulates glucocorticoid-induced corticohippocampal remodeling and behavioral despair
dc.typeJournal Article
dc.identifier.doi10.1038/tp.2017.205
melbourne.affiliation.departmentFlorey Department of Neuroscience and Mental Health
melbourne.affiliation.departmentPharmacology and Therapeutics
melbourne.source.titleTranslational Psychiatry
melbourne.source.volume7
melbourne.source.issue9
dc.rights.licenseCC BY
melbourne.elementsid1235325
melbourne.contributor.authorvan den Buuse, Maarten
melbourne.contributor.authorHill, Rachel
melbourne.contributor.authorDu, Xin
dc.identifier.eissn2158-3188
melbourne.accessrightsOpen Access


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