| Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. | |
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MedLine Citation:
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PMID: 21198979 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have evaluated the possibility that the action of voluntary exercise on the regulation of brain-derived neurotrophic factor (BDNF), a molecule important for rat hippocampal learning, could involve mechanisms of epigenetic regulation. We focused the studies on the Bdnf promoter IV, as this region is highly responsive to neuronal activity. We have found that exercise stimulates DNA demethylation in Bdnf promoter IV, and elevates levels of activated methyl-CpG-binding protein 2, as well as BDNF mRNA and protein in the rat hippocampus. Chromatin immunoprecipitation assay showed that exercise increases acetylation of histone H3, and protein assessment showed that exercise elevates the ratio of acetylated :total for histone H3 but had no effects on histone H4 levels. Exercise also reduces levels of the histone deacetylase 5 mRNA and protein implicated in the regulation of the Bdnf gene [N.M. Tsankova et al. (2006)Nat. Neurosci., 9, 519-525], but did not affect histone deacetylase 9. Exercise elevated the phosphorylated forms of calcium/calmodulin-dependent protein kinase II and cAMP response element binding protein, implicated in the pathways by which neural activity influences the epigenetic regulation of gene transcription, i.e. Bdnf. These results showing the influence of exercise on the remodeling of chromatin containing the Bdnf gene emphasize the importance of exercise on the control of gene transcription in the context of brain function and plasticity. Reported information about the impact of a behavior, inherently involved in the daily human routine, on the epigenome opens exciting new directions and therapeutic opportunities in the war against neurological and psychiatric disorders. |
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Authors:
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F Gomez-Pinilla; Y Zhuang; J Feng; Z Ying; G Fan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-12-31 |
Journal Detail:
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Title: The European journal of neuroscience Volume: 33 ISSN: 1460-9568 ISO Abbreviation: Eur. J. Neurosci. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-31 Completed Date: 2011-05-12 Revised Date: 2012-01-13 |
Medline Journal Info:
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Nlm Unique ID: 8918110 Medline TA: Eur J Neurosci Country: France |
Other Details:
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Languages: eng Pagination: 383-90 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. |
Affiliation:
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Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA. Fgomezpi@ucla.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Brain-Derived Neurotrophic Factor / biosynthesis, genetics* Chromatin Assembly and Disassembly / genetics Chromatin Immunoprecipitation DNA Methylation / genetics Epigenesis, Genetic / genetics* Gene Expression Gene Expression Regulation / genetics Hippocampus / physiology* Male Motor Activity / genetics Neuronal Plasticity / genetics* Physical Conditioning, Animal / physiology* Promoter Regions, Genetic / genetics Rats Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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NS50465/NS/NINDS NIH HHS; NS51411/NS/NINDS NIH HHS; NS56413/NS/NINDS NIH HHS; R01 NS050465-05/NS/NINDS NIH HHS; R01 NS056413-02/NS/NINDS NIH HHS; R01 NS056413-03/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Brain-Derived Neurotrophic Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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