TY  - JOUR
AU  - Notaras, M
AU  - Du, X
AU  - Gogos, J
AU  - van den Buuse, M
AU  - Hill, RA
Y2  - 2020/12/17
Y1  - 2017/09/19
SN  - 2158-3188
UR  - http://hdl.handle.net/11343/255095
AB  - The 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.
LA  - English
PB  - NATURE PUBLISHING GROUP
T1  - The BDNF Val66Met polymorphism regulates glucocorticoid-induced corticohippocampal remodeling and behavioral despair
DO  - 10.1038/tp.2017.205
IS  - Translational Psychiatry
VL  - 7
IS  - 9
L1  - /bitstream/handle/11343/255095/PMC5639248.pdf?sequence=1&isAllowed=y
ER  -