ARL Division of Neural Systems, Memory & Aging and Evelyn F McKnight Brain Institute, University of Arizona, Tucson, AZ 85724, USA.
Neurobiol Aging. 2011 Dec;32(12):2198-210. doi: 10.1016/j.neurobiolaging.2010.01.009. Epub 2010 Mar 1.
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.
支持记忆过程的基因转录可能会受到正常衰老过程的影响。由于 Arc 对于记忆巩固和持久的突触可塑性是必需的，我们在衰老的海马体中检查了 Arc 转录。在这里，我们报告说，与成年海马体相比，在“离线”休息期间和进行空间行为后，Arc 转录在衰老的海马体中减少。这种减少在 CA1“位置细胞”的集合中观察到，这些细胞的每个细胞产生的 mRNA 更少，在齿状回（DG）中，通过行为激活的颗粒细胞更少。此外，我们提供的数据表明，Arc 基因甲基化的异常变化可能是导致 CA1 和 DG 中 Arc 转录随年龄减少的原因。鉴于 Arc 对于正常的记忆功能是必需的，这些亚区特异性的表观遗传和转录变化可能导致在衰老过程中记忆存储和检索效率降低。
