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PMID: 20142488 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

BDNF variant Val66Met interacts with estrous cycle in the control of hippocampal function.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 9 ·2010-03-02 ·Pages 4395-400

Spencer JL, Waters EM, Milner TA, Lee FS, McEwen BS

Abstract

Natural fluctuations in circulating estradiol are associated with behavioral changes, including severe disturbances in mood and cognition in some women. Common genetic variation in some of the molecular mediators of estradiol effects on these behaviors, in brain regions such as the hippocampus, may explain individual variation in estradiol effects on behavior. We tested whether the common human variant BDNF Val66Met interacts with estradiol in the control of hippocampal function in cycling female mice homozygous for the wild-type Val or BDNF Met variant. BDNF Met increased anxiety behavior, impaired memory, and increased expression of BDNF and its receptor TrkB in the hippocampal formation. BDNF Met also dramatically altered the fluctuation of spatial memory, hippocampal Akt phosphorylation, and PSD-95 protein expression across the estrous cycle. The variant BDNF Val66Met should therefore be considered as a strong candidate for mediating genetic differences in ovarian steroid-related behavioral changes and disorders.

MeSH Terms
Animals Behavior, Animal Brain-Derived Neurotrophic Factor/chemistry,genetics,physiology Estrus/physiology Female Genotype Hippocampus/physiology Methionine/genetics Mice Valine/genetics
Chemicals
Brain-Derived Neurotrophic Factor Methionine Valine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Spencer Joanna L
Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065, USA. [email protected]
Waters Elizabeth M
Milner Teresa A
Lee Francis S
McEwen Bruce S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0915105107
Email
[email protected]
Published
2010-03-02
Epub
2010-00-08
Pages
4395-400
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2840147
Subset
IM
Grants
NINDS NIH HHS · NS07080 · United States
NIMH NIH HHS · MH079513 · United States
NINDS NIH HHS · R01 NS007080 · United States
NIMH NIH HHS · P50 MH079513 · United States
NIDA NIH HHS · R01 DA008259 · United States
NHLBI NIH HHS · P01 HL018974 · United States
NIMH NIH HHS · MH082528 · United States
NINDS NIH HHS · R01 NS052819 · United States
NIMH NIH HHS · F30 MH082528 · United States
NINDS NIH HHS · NS052819 · United States
NIGMS NIH HHS · T32 GM007739 · United States
NIDA NIH HHS · DA08259 · United States
NHLBI NIH HHS · HL18974 · United States
External Links
PubMed source DOI: 10.1073/pnas.0915105107 PMC Full Text View journal details
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