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

TitleGenetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior.
Publication TypeJournal Article
Year of Publication2006
AuthorsChen Z-Y, Jing D, Bath KG, Ieraci A, Khan T, Siao C-J, Herrera DG, Toth M, Yang C, McEwen BS, Hempstead BL, Lee FS
JournalScience
Volume314
Issue5796
Pagination140-3
Date Published2006 Oct 06
ISSN1095-9203
KeywordsAlleles, Animals, Anxiety, Behavior, Animal, Brain-Derived Neurotrophic Factor, Conditioning (Psychology), Dendrites, Dentate Gyrus, Fear, Fluoxetine, Hippocampus, Memory, Mice, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Neurons, Organ Size, Polymorphism, Single Nucleotide, Rats, Rats, Sprague-Dawley, Serotonin Uptake Inhibitors
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.

DOI10.1126/science.1129663
Alternate JournalScience
PubMed ID17023662
PubMed Central IDPMC1880880
Grant ListNS30687 / NS / NINDS NIH HHS / United States
R01 NS052819 / NS / NINDS NIH HHS / United States
MH068850 / MH / NIMH NIH HHS / United States
MH060478 / MH / NIMH NIH HHS / United States
NS052819 / NS / NINDS NIH HHS / United States