Age-related changes in Arc transcription and DNA methylation within the hippocampus

NEUROBIOLOGY OF AGING

卷:32

Article

Penner, M. R.^1,2  Roth, T. L.^3,4  Chawla, M. K.^1,2  Hoang, L. T.^1,2  Roth, E. D.^3,4  Lubin, F. D.^3,4  Sweatt, J. D.^3,4  Worley, P. F.^5,6  Barnes, C. A.^1,2,7,8 

[1] Univ Arizona, Evelyn F McKnight Brain Inst, Tucson, AZ 85724 USA

[2] Univ Arizona, ARL Div Neural Syst Memory & Aging, Tucson, AZ 85724 USA

[3] Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL USA

[4] Univ Alabama Birmingham, Evelyn F McKnight Brain Inst, Birmingham, AL USA

[5] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA

[6] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA

[7] Univ Arizona, Dept Psychol, Tucson, AZ 85724 USA

[8] Univ Arizona, Dept Neurol, Tucson, AZ 85724 USA

关键词: Immediate-early gene;    Epigenetics;    Normal aging;    Hippocampus;   

DOI  :  10.1016/j.neurobiolaging.2010.01.009

来源: Elsevier

【 摘 要 】

The transcription of genes that support memory processes are likely to be impacted by the normal aging process. Because Arc is necessary for memory consolidation and enduring synaptic plasticity, we examined Arc transcription within the aged hippocampus. Here, we report that Arc transcription is reduced within the aged hippocampus compared to the adult hippocampus during both off line periods of rest, and following spatial behavior. This reduction is observed within ensembles of CA1 place cells, which make less mRNA per cell, and in the dentate gyrus (DG) where fewer granule cells are activated by behavior. In addition, we present data suggesting that aberrant changes in methylation of the Arc gene may be responsible for age-related decreases in Arc transcription within CA1 and the DG. Given that Arc is necessary for normal memory function, these subregion-specific epigenetic and transcriptional changes may result in less efficient memory storage and retrieval during aging. (C) 2010 Elsevier Inc. All rights reserved.

【 授权许可】

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