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

Penner, M.R.; Roth, T.L.; Chawla, M.K.; Hoang, L.T.; Roth, E.D.; Lubin, F.D.; Sweatt, J.D.; Worley, P.F.; Barnes, C.A.

doi:10.1016/j.neurobiolaging.2010.01.009

« Previous Next »Neurobiology of Aging
Volume 32, Issue 12 , Pages 2198-2210, December 2011

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

M.R. Penner
- ARL Div of Neural Systems, Memory & Aging and Evelyn F McKnight Brain Institute, Univ Arizona, Tucson, AZ, United States
T.L. Roth
- Department of Neurobiology and Evelyn F McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL, United States
M.K. Chawla
- ARL Div of Neural Systems, Memory & Aging and Evelyn F McKnight Brain Institute, Univ Arizona, Tucson, AZ, United States
L.T. Hoang
- ARL Div of Neural Systems, Memory & Aging and Evelyn F McKnight Brain Institute, Univ Arizona, Tucson, AZ, United States
E.D. Roth
- Department of Neurobiology and Evelyn F McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL, United States
F.D. Lubin
- Department of Neurobiology and Evelyn F McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL, United States
J.D. Sweatt
- Department of Neurobiology and Evelyn F McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL, United States
P.F. Worley
- Departments of Neuroscience & Neurology, Johns Hopkins University, Baltimore, MD, United States
C.A. Barnes
- ARL Div of Neural Systems, Memory & Aging and Evelyn F McKnight Brain Institute, Univ Arizona, Tucson, AZ, United States
- Departments of Psychology & Neurology, University of Arizona, Tucson, AZ, United States
- Corresponding author at: University of Arizona, Evelyn F McKnight Brain Institute, Life Sciences North, Rm 362, Tucson, AZ 85724, United States. Tel.: +1 520 626 2616; fax: +1 520 626 2618.

Received 2 September 2009; received in revised form 12 January 2010; accepted 14 January 2010. published online 02 March 2010.

Abstract

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.

Keywords: Immediate-early gene, Epigenetics, Normal aging, Hippocampus