Title | Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. |
Publication Type | Journal Article |
Year of Publication | 2006 |
Authors | Chen 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 |
Journal | Science |
Volume | 314 |
Issue | 5796 |
Pagination | 140-3 |
Date Published | 2006 Oct 06 |
ISSN | 1095-9203 |
Keywords | Alleles, 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. |
DOI | 10.1126/science.1129663 |
Alternate Journal | Science |
PubMed ID | 17023662 |
PubMed Central ID | PMC1880880 |
Grant List | NS30687 / 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 |