title: Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior.
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.
authors.affiliation: Department of Psychiatry, Weill Medical College of Cornell University, New York, NY 10021, USA. zheyuchen@sdu.edu.cn
authors.forename: Zhe-Yu
authors.initials: ZY
authors.lastname: Chen
authors.forename: Deqiang
authors.initials: D
authors.lastname: Jing
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Bath
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ieraci
authors.forename: Tanvir
authors.initials: T
authors.lastname: Khan
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Siao
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Herrera
authors.forename: Miklos
authors.initials: M
authors.lastname: Toth
authors.forename: Chingwen
authors.initials: C
authors.lastname: Yang
authors.forename: Bruce S
authors.initials: BS
authors.lastname: McEwen
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Hempstead
authors.forename: Francis S
authors.initials: FS
authors.lastname: Lee
mesh_terms: D000483:Alleles; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics*; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000502:physiology*; D003213:Conditioning, Psychological; D003712:Dendrites / Q000648:ultrastructure; D018891:Dentate Gyrus / Q000166:cytology; D005239:Fear; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors