Impact of genetic variant BDNF (Val66Met) on brain structure and function. Review uri icon

Overview

abstract

  • A common single-nucleotide polymorphism in the human 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. Variant BDNF(Met) was expressed in brain at normal levels, but its secretion from neurons was defective. In this context, the BDNF(Met/Met) mouse represents a unique model that directly links altered activity-dependent release of BDNF to a defined set of in vivo consequences. Our subsequent analyses of these mice elucidated a phenotype that had not been established in human carriers: increased anxiety. When placed in conflict settings, BDNF(Met/Met) mice display increased anxiety-related behaviours that were not normalized by the antidepressant, fluoxetine. A genetic variant BDNF may thus play a key role in genetic predispositions to anxiety and depressive disorders.

publication date

  • January 1, 2008

Research

keywords

  • Anxiety Disorders
  • Brain
  • Brain-Derived Neurotrophic Factor
  • Depressive Disorder
  • Genetic Variation
  • Mental Disorders
  • Polymorphism, Single Nucleotide

Identity

PubMed Central ID

  • PMC2735856

Scopus Document Identifier

  • 48849109122

Digital Object Identifier (DOI)

  • 10.1002/9780470751251.ch14

PubMed ID

  • 18497103

Additional Document Info

volume

  • 289