基因变体脑源性神经营养因子（Val66Met）多态性改变焦虑相关行为。
Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior.
作者信息
Chen Zhe-Yu, 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
机构信息
Department of Psychiatry, Weill Medical College of Cornell University, New York, NY 10021, USA.
出版信息
Science. 2006 Oct 6;314(5796):140-3. doi: 10.1126/science.1129663.
Abstract
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.
摘要
脑源性神经营养因子（BDNF）基因中一种常见的单核苷酸多态性，即第66位密码子处缬氨酸（Val）被蛋氨酸（Met）取代（Val66Met），与脑解剖结构和记忆的改变有关，但其与临床疾病的相关性尚不清楚。我们培育了一种携带变异BDNF的小鼠（BDNF(Met/Met)），该小鼠再现了携带变异等位基因人类的表型特征。BDNF(Met)在脑中的表达水平正常，但其从神经元的分泌存在缺陷。当置于应激环境中时，BDNF(Met/Met)小鼠表现出与焦虑相关的行为增加，且抗抑郁药氟西汀无法使其恢复正常。因此，变异的BDNF可能在焦虑症和抑郁症的遗传易感性中起关键作用。
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