Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity.
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.
Lipsky
Robert H
RH
Section of Molecular Genetics, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20814, USA.
Marini
Ann M
AM
D001526:Behavioral Symptoms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D008568:Memory / Q000502:physiology; D009154:Mutation; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor