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

被引：3184

作者：

Egan, MF

Kojima, M

Callicott, JH

Goldberg, TE

Kolachana, BS

Bertolino, A

Zaitsev, E

Gold, B

Goldman, D

Dean, M

Lu, B

Weinberger, DR

机构：

[1] NICHHD, Sect Neural Dev & Plast, NIH, DHHS, Bethesda, MD 20892 USA

[2] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA

[3] NIAAA, Neurogenet Lab, Rockville, MD 20857 USA

[4] NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA

[5] Natl Inst AIST, Cell Dynam Res Grp, Osaka 5638577, Japan

[6] Japan Sci & Technol Corp, CREST, Kawaguchi 3320012, Japan

来源：

CELL | 2003年 / 112卷 / 02期

关键词：

D O I：

10.1016/S0092-8674(03)00035-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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

引用

页码：257 / 269

页数：13

共 52 条

[41] INTRINSIC SIGNAL CHANGES ACCOMPANYING SENSORY STIMULATION - FUNCTIONAL BRAIN MAPPING WITH MAGNETIC-RESONANCE-IMAGING [J].