RT Journal Article
SR Electronic
T1 Variant Brain-Derived Neurotrophic Factor Val66Met Polymorphism Alters Vulnerability to Stress and Response to Antidepressants
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4092
OP 4101
DO 10.1523/JNEUROSCI.5048-11.2012
VO 32
IS 12
A1 Yu, Hui
A1 Wang, Dong-Dong
A1 Wang, Yue
A1 Liu, Ting
A1 Lee, Francis S.
A1 Chen, Zhe-Yu
YR 2012
UL http://www.jneurosci.org/content/32/12/4092.abstract
AB Brain-derived neurotrophic factor (BDNF) plays important roles in cell survival, neural plasticity, learning, and stress regulation. However, whether the recently found human BDNF Val66Met (BDNFMet) polymorphism could alter stress vulnerability remains controversial. More importantly, the molecular and structural mechanisms underlying the interaction between the BDNFMet polymorphism and stress are unclear. We found that heterozygous BDNF+/Met mice displayed hypothalamic-pituitary-adrenal axis hyperreactivity, increased depressive-like and anxiety-like behaviors, and impaired working memory compared with WT mice after 7 d restraint stress. Moreover, BDNF+/Met mice exhibited more prominent changes in BDNF levels and apical dendritic spine density in the prefrontal cortex and amygdala after stress, which correlated with the impaired working memory and elevated anxiety-like behaviors. Finally, the depressive-like behaviors in BDNF+/Met mice could be selectively rescued by acute administration of desipramine but not fluoxetine. These data indicate selective behavioral, molecular, and structural deficits resulting from the interaction between stress and the human genetic BDNFMet polymorphism. Importantly, desipramine but not fluoxetine has antidepressant effects on BDNF+/Met mice, suggesting that specific classes of antidepressant may be a more effective treatment option for depressive symptoms in humans with this genetic variant BDNF.