On March 21, the Journal of Neuroscience published a research article entitled “Variant Brain-Derived Neurotrophic Factor Val66Met Polymorphism Alters Vulnerability to Stress and Response to Antidepressants”, which was recommended as a featured paper in the journal. The work was carried out by lecturer Yu Hui, graduate student Wang Dongdong and colleagues in the Department of Neurobiology, under the supervision of Prof. Chen Zheyu.

Brain-derived neurotrophic factor (BDNF) plays an important role 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.

This paper reported that heterozygousBDNF^+/Metmice displayed hypothalamic-pituitary-adrenal axis hyperreactivity, increased depressive-like and anxiety-like behaviors, and impaired working memory compared with WT mice after stress. Moreover,BDNF^+/Metmice exhibited more prominent changes in BDNF levels and dendritic spine density in different brain regions after stress. Finally, the depressive-like behaviors inBDNF^+/Metmice could be selectively cured by acute administration of desipramine but not fluoxetine. This data suggests that specific classes of antidepressant may be a more effective treatment option for depressive symptoms in humans with genetic variant BDNF.

This study was supported by grants from the National Natural Science Foundation of China and the National 973 Basic Research Program of China.

BDNFMet polymorphism increased susceptibility to stress by the hyperreactive HPA axis activity, altered BDNF levels and dendritic spine density in different brain regions.

Written by: Liu Ting

Edited by: Lawrence Phillips, Jing Zizhao

Source: School of Medicine,www.view.sdu.edu.cn