期刊
NEUROSCIENTIST
卷 18, 期 5, 页码 439-451出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1073858411431646
关键词
brain-derived neurotrophic factor Val66Met; single-nucleotide polymorphism; learning and memory; animal model; synaptic plasticity
资金
- DeWitt-Wallace Fund of the New York Community Trust
- Irma T. Hirschl/Monique Weill-Caulier Trust
- International Mental Health Research Organization
- Burroughs Wellcome Foundation
- Pritzker Consortium
- NARSAD
- National Institutes of Health [NS052819, MH088814]
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factor family and is implicated as a modulator of neuronal survival and differentiation, synaptic plasticity, and higher order cognitive functions such as learning and memory. A common single-nucleotide polymorphism (SNP) has been identified in the human BDNF gene (BDNF Val66Met) that leads to decreased BDNF secretion and impairments in specific forms of learning in humans. To better understand the impact of this SNP on biological function, the authors generated a mouse model containing the BDNF Met allele, which they found to replicate the key phenotypes observed in humans and provided further insight into the functional impact of this SNP in vivo. They used a bottom-up approach to study the BDNF SNP, which provided external validation in biologically less complex, genetically uniform systems, which minimized the variability inherent in human studies. In this review, the authors discuss the impact of the BDNF SNP on learning and memory while providing arguments for the relevance of a vertically integrated approach to studying human genetic variants.
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