Genetic Variant BDNF (Val66Met) Polymorphism Alters Anxiety-Related Behavior-Reference-Cited by-同舟云学术

Genetic Variant BDNF (Val66Met) Polymorphism Alters Anxiety-Related Behavior

Published:2006-10-06 Issue:5796 Volume:314 Page:140-143
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Chen Zhe-Yu¹²³⁴⁵,Jing Deqiang¹²³⁴⁵,Bath Kevin G.¹²³⁴⁵,Ieraci Alessandro¹²³⁴⁵,Khan Tanvir¹²³⁴⁵,Siao Chia-Jen¹²³⁴⁵,Herrera Daniel G.¹²³⁴⁵,Toth Miklos¹²³⁴⁵,Yang Chingwen¹²³⁴⁵,McEwen Bruce S.¹²³⁴⁵,Hempstead Barbara L.¹²³⁴⁵,Lee Francis S.¹²³⁴⁵

Affiliation:

1. Department of Psychiatry, Weill Medical College of Cornell University, New York, NY 10021, USA.

2. Division of Hematology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.

3. Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021, USA.

4. School of Medicine, Shandong University, Jinan, Shandong 250012, People's Republic of China.

5. Gene Targeting Facility, The Rockefeller University, New York, NY 10021, USA.

Abstract

A common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met), is associated with alterations in brain anatomy and memory, but its relevance to clinical disorders is unclear. We generated a variant BDNF mouse (BDNF Met/Met ) that reproduces the phenotypic hallmarks in humans with the variant allele. BDNF Met was expressed in brain at normal levels, but its secretion from neurons was defective. When placed in stressful settings, BDNF Met/Met mice exhibited increased anxiety-related behaviors that were not normalized by the antidepressant, fluoxetine. A variant BDNF may thus play a key role in genetic predispositions to anxiety and depressive disorders.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference30 articles.

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