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

Full 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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Author information

Author/s: Egan, Michael F (MF); Kojima, Masami (M); Callicott, Joseph H (JH); Goldberg, Terry E (TE); Kolachana, Bhaskar S (BS); Bertolino, Alessandro (A); Zaitsev, Eugene (E); Gold, Bert (B); Goldman, David (D); Dean, Michael (M); Lu, Bai (B); Weinberger, Daniel R (DR);

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

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Cell (Cell), published in United States. (Language: eng)

Reference: 2003-Jan; vol 112 (issue 2) : pp 257-69

Dates: Created 2003/01/29; Completed 2003/02/14; Revised 2006/11/15;

PMID: 12553913, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: Cell. 2003 Jan 24;112(2):144-5. (PMID: 12553902)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Alleles
Aspartic Acid - analogs & derivatives; metabolism
Brain-Derived Neurotrophic Factor - genetics; secretion
Cells, Cultured
Dendrites - metabolism; secretion
Female
Hippocampus - cytology; physiology
Humans
Magnetic Resonance Imaging
Male

Memory - physiology
Methionine - genetics
Microscopy, Fluorescence
Neurons - cytology; metabolism; secretion
Point Mutation - genetics
Polymorphism, Single Nucleotide - genetics
Protein Transport
Secretory Vesicles - metabolism
Synapses - metabolism
Valine - genetics

Associated Chemicals: Brain-Derived Neurotrophic Factor (0) ; Aspartic Acid (56-84-8) ; Methionine (63-68-3) ; Valine (7004-03-7) ; N-acetylaspartate (997-55-7)

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