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 Weinberger

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)257-269
Number of pages13
JournalCell
Volume112
Issue number2
DOIs
StatePublished - Jan 24 2003
Externally publishedYes

Fingerprint

Brain-Derived Neurotrophic Factor
Polymorphism
Methionine
Data storage equipment
Valine
Episodic Memory
Depolarization
Nerve Growth Factors
Secretory Vesicles
Aspartic Acid
Synapses
Magnetic resonance imaging
Neurons
Plasticity
human brain-derived neurotrophic factor
Spectrum Analysis
Animals
Substitution reactions
Animal Models
Chemical activation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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

In: Cell, Vol. 112, No. 2, 24.01.2003, p. 257-269.

Research output: Contribution to journalArticle

Egan, MF, Kojima, M, Callicott, JH, Goldberg, TE, Kolachana, BS, Bertolino, A, Zaitsev, E, Gold, B, Goldman, D, Dean, M, Lu, B & Weinberger, D 2003, 'The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function', Cell, vol. 112, no. 2, pp. 257-269. https://doi.org/10.1016/S0092-8674(03)00035-7
Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003 Jan 24;112(2):257-269. https://doi.org/10.1016/S0092-8674(03)00035-7
Egan, Michael F. ; Kojima, Masami ; Callicott, Joseph H. ; Goldberg, Terry E. ; Kolachana, Bhaskar S. ; Bertolino, Alessandro ; Zaitsev, Eugene ; Gold, Bert ; Goldman, David ; Dean, Michael ; Lu, Bai ; Weinberger, Daniel. / The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. In: Cell. 2003 ; Vol. 112, No. 2. pp. 257-269.
@article{0968a62427ba49b6b72a8d192ad82924,
title = "The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function",
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.",
author = "Egan, {Michael F.} and Masami Kojima and Callicott, {Joseph H.} and Goldberg, {Terry E.} and Kolachana, {Bhaskar S.} and Alessandro Bertolino and Eugene Zaitsev and Bert Gold and David Goldman and Michael Dean and Bai Lu and Daniel Weinberger",
year = "2003",
month = "1",
day = "24",
doi = "10.1016/S0092-8674(03)00035-7",
language = "English (US)",
volume = "112",
pages = "257--269",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function

AU - Egan, Michael F.

AU - Kojima, Masami

AU - Callicott, Joseph H.

AU - Goldberg, Terry E.

AU - Kolachana, Bhaskar S.

AU - Bertolino, Alessandro

AU - Zaitsev, Eugene

AU - Gold, Bert

AU - Goldman, David

AU - Dean, Michael

AU - Lu, Bai

AU - Weinberger, Daniel

PY - 2003/1/24

Y1 - 2003/1/24

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0037462449&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037462449&partnerID=8YFLogxK

U2 - 10.1016/S0092-8674(03)00035-7

DO - 10.1016/S0092-8674(03)00035-7

M3 - Article

C2 - 12553913

AN - SCOPUS:0037462449

VL - 112

SP - 257

EP - 269

JO - Cell

JF - Cell

SN - 0092-8674

IS - 2

ER -