Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior.
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.
Chen
Zhe-Yu
ZY
Department of Psychiatry, Weill Medical College of Cornell University, New York, NY 10021, USA. zheyuchen@sdu.edu.cn
Jing
Deqiang
D
Bath
Kevin G
KG
Ieraci
Alessandro
A
Khan
Tanvir
T
Siao
Chia-Jen
CJ
Herrera
Daniel G
DG
Toth
Miklos
M
Yang
Chingwen
C
McEwen
Bruce S
BS
Hempstead
Barbara L
BL
Lee
Francis S
FS
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
D019208:Brain-Derived Neurotrophic Factor; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors