标题：Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior
作者：Chen ZY;Jing DQ;Bath KG;Ieraci A;Khan T;Siao CJ;Herrera DG;Toth M;Yang C;McEwen BS
作者机构：[Chen, Z.-Y] Department of Psychiatry, Weill Medical College of Cornell University, New York, NY 10021, United States, School of Medicine, Shandong Un 更多
通讯作者地址：[Chen, ZY]Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY 10021 USA.
关键词：ACTIVITY-DEPENDENT SECRETION;NEUROTROPHIC FACTOR;HIPPOCAMPAL FUNCTION;ANIMAL-MODELS;HUMAN-MEMORY;BRAIN;DEPRESSION;MICE;NEURONS;TRAITS
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 (BDNFMet/Met) that reproduces the phenotypic hallmarks in humans with the variant allele. BDNFMet was expressed in brain at normal levels, but its secretion from neurons was defective. When placed in stressful settings, BDNFMet/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.