Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior

被引：1044

作者：

Chen, Zhe-Yu ^{[1
]}

Jing, Deqiang

Bath, Kevin G.

Ieraci, Alessandro

Khan, Tanvir

Siao, Chia-Jen

Herrera, Daniel G.

Toth, Miklos

Yang, Chingwen

McEwen, Bruce S.

Hempstead, Barbara L.

Lee, Francis S.

机构：

[1] Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY 10021 USA

[2] Cornell Univ, Weill Med Coll, Dept Med, Div Hematol, New York, NY 10021 USA

[3] Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA

[4] Shandong Univ, Sch Med, Jinan 250012, Shandong, Peoples R China

[5] Rockefeller Univ, Gene Targeting Facil, New York, NY 10021 USA

[6] Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA

来源：

SCIENCE | 2006年 / 314卷 / 5796期

关键词：

D O I：

10.1126/science.1129663

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A common single-nucleotide polymorphism in the brain-derived neurotrophic factor ( BDNF) gene, a methionine ( Met) substitution for valine (Val) at codon 66 (Val66Met), is associated with alterations in brain anatomy and memory, but its relevance to clinical disorders is unclear. We generated a variant BDNF mouse (BDNF(Met/Met)) that reproduces the phenotypic hallmarks in humans with the variant allele. BDNF(Met) was expressed in brain at normal levels, but its secretion from neurons was defective. When placed in stressful settings, BDNF(Met/Met) mice exhibited increased anxiety-related behaviors that were not normalized by the antidepressant, fluoxetine. A variant BDNF may thus play a key role in genetic predispositions to anxiety and depressive disorders.

引用

页码：140 / 143

页数：4

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