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Cell. 2003 Jan 24;112(2):257-69.

The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function.

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  • 1Clinical Brain Disorders Branch, National Institute of Mental Health, Room 4s-235, 10 Center Drive, Bethesda, MD 20892, USA.

Abstract

Brain-derived neurotrophic factor (BDNF) modulates hippocampal plasticity and hippocampal-dependent memory in cell models and in animals. We examined the effects of a valine (val) to methionine (met) substitution in the 5' pro-region of the human BDNF protein. In human subjects, the met allele was associated with poorer episodic memory, abnormal hippocampal activation assayed with fMRI, and lower hippocampal n-acetyl aspartate (NAA), assayed with MRI spectroscopy. Neurons transfected with met-BDNF-GFP showed lower depolarization-induced secretion, while constitutive secretion was unchanged. Furthermore, met-BDNF-GFP failed to localize to secretory granules or synapses. These results demonstrate a role for BDNF and its val/met polymorphism in human memory and hippocampal function and suggest val/met exerts these effects by impacting intracellular trafficking and activity-dependent secretion of BDNF.

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PMID:
12553913
[PubMed - indexed for MEDLINE]
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