The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function
Michael F Egan, Masami Kojima, Joseph H Callicott, Terry E Goldberg, Bhaskar S Kolachana, Alessandro Bertolino, Eugene Zaitsev, Bert Gold, David Goldman, Michael Dean, Bai Lu, Daniel R Weinberger, Michael F Egan, Masami Kojima, Joseph H Callicott, Terry E Goldberg, Bhaskar S Kolachana, Alessandro Bertolino, Eugene Zaitsev, Bert Gold, David Goldman, Michael Dean, Bai Lu, Daniel R Weinberger
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.
Source: PubMed