The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function.
Cell
; 112(2): 257-69, 2003 Jan 24.
Article
em En
| MEDLINE
| ID: mdl-12553913
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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Base de dados:
MEDLINE
Assunto principal:
Valina
/
Ácido Aspártico
/
Fator Neurotrófico Derivado do Encéfalo
/
Polimorfismo de Nucleotídeo Único
/
Hipocampo
/
Memória
/
Metionina
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Cell
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos