title: Variant brain-derived neurotrophic factor (Valine66Methionine) polymorphism contributes to developmental and estrous stage-specific expression of anxiety-like behavior in female mice.
abstract: BACKGROUND
  Most anxiety and depressive disorders are twice as common in women compared with men, and the sex difference in prevalence typically emerges during adolescence. Hormonal changes across the menstrual cycle and during the postpartum and perimenopausal periods are associated with increased risk for anxiety and depression symptoms. In humans and animals, reduced brain-derived neurotrophic factor (BDNF) has been associated with increased expression of affective pathology. Recently, a single nucleotide polymorphism (SNP) in the BDNF gene (BDNF Valine66Methionine [Val66Met]), which reduces BDNF bioavailability, has been identified in humans and associated with a variety of neuropsychiatric disorders. Although BDNF expression can be directly influenced by estrogen and progesterone, the potential impact of the BDNF Val66Met SNP on sensitivity to reproductive hormone changes remains an open question.
  
  
  METHODS
  As a predictive model, we used female mice in which the human SNP (BDNF Val66Met) was inserted into the mouse BDNF gene. Using standard behavioral paradigms, we tested the impact of this SNP on age and estrous-cycle-specific expression of anxiety-like behaviors.
  
  
  RESULTS
  Mice homozygous for the BDNF Val66Met SNP begin to exhibit increased anxiety-like behaviors over prepubertal and early adult development, show significant fluctuations in anxiety-like behaviors over the estrous cycle, and, as adults, differ from wild-type mice by showing significant fluctuations in anxiety-like behaviors over the estrous cycle-specifically, more anxiety-like behaviors during the estrus phase.
  
  
  CONCLUSIONS
  These findings have implications regarding the potential role of this SNP in contributing to developmental and reproductive hormone-dependent changes in affective disorders in humans.
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Bath
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Chuang
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Spencer-Segal
authors.forename: Dima
authors.initials: D
authors.lastname: Amso
authors.forename: Margaret
authors.initials: M
authors.lastname: Altemus
authors.forename: Bruce S
authors.initials: BS
authors.lastname: McEwen
authors.forename: Francis S
authors.initials: FS
authors.lastname: Lee
mesh_terms: D000483:Alleles; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004195:Disease Models, Animal; D004971:Estrus / Q000235:genetics*; D005260:Female; D051379:Mice; D016254:Mutagenesis, Insertional; D020641:Polymorphism, Single Nucleotide; D012741:Sexual Maturation / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor