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Brain‐Derived Neurotrophic Factor in Neuronal Survival and Behavior‐Related Plasticity
Author(s) -
LIPSKY ROBERT H.,
MARINI ANN M.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1403.009
Subject(s) - neurotrophic factors , tropomyosin receptor kinase b , neurotrophin , brain derived neurotrophic factor , neuroscience , biology , hippocampal formation , receptor , psychology , genetics
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.