Genetic Variant BDNF (Val66Met) Polymorphism Alters Anxiety-Related Behavior
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- 6 October 2006
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 314 (5796) , 140-143
- https://doi.org/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.Keywords
This publication has 30 references indexed in Scilit:
- The brain-derived neurotrophic factor Val66Met polymorphism is associated with sense of coherence in a non-clinical community sample of 7335 adultsJournal of Psychiatric Research, 2007
- Severe deficits in 5‐HT2A‐mediated neurotransmission in BDNF conditional mutant miceJournal of Neurobiology, 2006
- Sortilin Controls Intracellular Sorting of Brain-Derived Neurotrophic Factor to the Regulated Secretory PathwayJournal of Neuroscience, 2005
- BDNF Variation and Mood Disorders: A Novel Functional Promoter Polymorphism and Val66Met are Associated with Anxiety but Have Opposing EffectsNeuropsychopharmacology, 2005
- Recent advances in animal models of chronic antidepressant effects: The novelty-induced hypophagia testNeuroscience & Biobehavioral Reviews, 2005
- The Brain-Derived Neurotrophic Factor val66met Polymorphism and Variation in Human Cortical MorphologyJournal of Neuroscience, 2004
- Requirement of Hippocampal Neurogenesis for the Behavioral Effects of AntidepressantsScience, 2003
- Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT GeneScience, 2003
- The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal FunctionPublished by Elsevier ,2003
- Conditional Deletion Of Brain-Derived Neurotrophic Factor in the Postnatal Brain Leads to Obesity and HyperactivityMolecular Endocrinology, 2001