PMID- 25836028 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150403 LR - 20220317 IS - 2079-7737 (Print) IS - 2079-7737 (Electronic) IS - 2079-7737 (Linking) VI - 4 IP - 2 DP - 2015 Apr 1 TI - Environmental enrichment reverses histone methylation changes in the aged hippocampus and restores age-related memory deficits. PG - 298-313 LID - 10.3390/biology4020298 [doi] AB - 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. FAU - Morse, Sarah J AU - Morse SJ AD - Department of Neurobiology, The Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, AL 35294, USA. umbraphiles@gmail.com. FAU - Butler, Anderson A AU - Butler AA AD - Department of Neurobiology, The Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, AL 35294, USA. aabutler@uab.edu. FAU - Davis, Robin L AU - Davis RL AD - Department of Neurobiology, The Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, AL 35294, USA. robinlynndavis@gmail.com. FAU - Soller, Ian J AU - Soller IJ AD - Department of Neurobiology, The Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, AL 35294, USA. ijsoller@uab.edu. FAU - Lubin, Farah D AU - Lubin FD AD - Department of Neurobiology, The Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, AL 35294, USA. flubin@uab.edu. LA - eng GR - P30 HD038985/HD/NICHD NIH HHS/United States GR - K99 MH082106/MH/NIMH NIH HHS/United States GR - T32 NS061788/NS/NINDS NIH HHS/United States GR - R01 MH097909/MH/NIMH NIH HHS/United States GR - R00 MH082106/MH/NIMH NIH HHS/United States PT - Journal Article DEP - 20150401 PL - Switzerland TA - Biology (Basel) JT - Biology JID - 101587988 PMC - PMC4498301 EDAT- 2015/04/04 06:00 MHDA- 2015/04/04 06:01 PMCR- 2015/06/01 CRDT- 2015/04/04 06:00 PHST- 2015/01/17 00:00 [received] PHST- 2015/03/10 00:00 [revised] PHST- 2015/03/19 00:00 [accepted] PHST- 2015/04/04 06:00 [entrez] PHST- 2015/04/04 06:00 [pubmed] PHST- 2015/04/04 06:01 [medline] PHST- 2015/06/01 00:00 [pmc-release] AID - biology4020298 [pii] AID - biology-04-00298 [pii] AID - 10.3390/biology4020298 [doi] PST - epublish SO - Biology (Basel). 2015 Apr 1;4(2):298-313. doi: 10.3390/biology4020298.