Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity

Ann N Y Acad Sci. 2007 Dec;1122:130-43. doi: 10.1196/annals.1403.009.

Abstract

Neurotrophins are critical to the development and maintenance of the mammalian central nervous system. Among them is brain-derived neurotrophic factor (BDNF), whose synthesis and release is targeted by activation of glutamate receptors. Perturbation of this process probably underlies neurodegenerative and psychiatric disorders. A naturally occurring variation in humans, in the form of a common single-nucleotide polymorphism in the pro region of the polypeptide at codon 66 (Val66-->Met), affects processing of the pro-BDNF polypeptide and its activation-dependent release. This variant is associated with differences in the volume of the hippocampal formation and with anxiety and depression-related phenotypes. Convergent findings supporting a role for BDNF in alterations to hippocampal structure and behavior are found in a "humanized" BDNF transgenic mouse. Also, recent human genetic studies have supported a role of BDNF signaling in addictive behaviors by allele-, genotype-, and haplotype-based association of the TrkB gene, which encodes the cognate receptor for BDNF, with alcohol dependence. A better understanding of the influence of BDNF-mediated pathways in cell survival and plasticity will aid in developing new approaches to restoring normal function in disease states.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Behavioral Symptoms* / genetics
  • Behavioral Symptoms* / pathology
  • Behavioral Symptoms* / physiopathology
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Survival / physiology
  • Humans
  • Memory / physiology
  • Mutation
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology*
  • Neurons / pathology
  • Neurons / physiology*

Substances

  • Brain-Derived Neurotrophic Factor