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Biology 2015, 4(2), 298-313; doi:10.3390/biology4020298

Environmental Enrichment Reverses Histone Methylation Changes in the Aged Hippocampus and Restores Age-Related Memory Deficits

Department of Neurobiology, The Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, AL 35294, USA
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Academic Editor: Bertram Opitz
Received: 17 January 2015 / Revised: 10 March 2015 / Accepted: 19 March 2015 / Published: 1 April 2015
(This article belongs to the Special Issue Neural Mechanisms of Learning and Memory)
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Abstract

A decline in long-term memory (LTM) formation is a common feature of the normal aging process, which corresponds with abnormal expression of memory-related genes in the aged hippocampus. Epigenetic modulation of chromatin structure is required for proper transcriptional control of genes, such as the brain-derived neurotrophic factor (Bdnf) and Zif268 in the hippocampus during the consolidation of new memories. Recently, the view has emerged that aberrant transcriptional regulation of memory-related genes may be reflective of an altered epigenetic landscape within the aged hippocampus, resulting in memory deficits with aging. Here, we found that baseline resting levels for tri-methylation of histone H3 at lysine 4 (H3K4me3) and acetylation of histone H3 at lysine 9 and 14 (H3K9,K14ac) were altered in the aged hippocampus as compared to levels in the hippocampus of young adult rats. Interestingly, object learning failed to increase activity-dependent H3K4me3 and di-methylation of histone H3 at lysine 9 (H3K9me2) levels in the hippocampus of aged adults as compared to young adults. Treatment with the LSD-1 histone demethylase inhibitor, t-PCP, increased baseline resting H3K4me3 and H3K9,K14ac levels in the young adult hippocampus, while young adult rats exhibited similar memory deficits as observed in aged rats. After environmental enrichment (EE), we found that object learning induced increases in H3K4me3 levels around the Bdnf, but not the Zif268, gene region in the aged hippocampus and rescued memory deficits in aged adults. Collectively, these results suggest that histone lysine methylation levels are abnormally regulated in the aged hippocampus and identify histone lysine methylation as a transcriptional mechanism by which EE may serve to restore memory formation with aging. View Full-Text
Keywords: epigenetics; histone acetylation; gene expression; memory; chromatin remodeling; hippocampus; methyltransferases; demethylases epigenetics; histone acetylation; gene expression; memory; chromatin remodeling; hippocampus; methyltransferases; demethylases
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Morse, S.J.; Butler, A.A.; Davis, R.L.; Soller, I.J.; Lubin, F.D. Environmental Enrichment Reverses Histone Methylation Changes in the Aged Hippocampus and Restores Age-Related Memory Deficits. Biology 2015, 4, 298-313.

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