Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior.
Journal:
Science 2006 OctAuthors:
Chen ZY, Jing D, Bath KG, Ieraci A, Khan T, Siao CJ, Herrera DG, Toth M, Yang C, McEwen BS, Hempstead BL, Lee FS
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
...[more]. 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.[less]
Mesh Headings:
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