期刊
NEUROBIOLOGY OF AGING
卷 36, 期 5, 页码 1868-1880出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.01.012
关键词
Microarray; Ingenuity pathway analysis; Transcription factors; synaptic protein synthesis
资金
- Royal Society of New Zealand Marsden Fund [UOO307]
- Health Research Council of New Zealand
- University of Otago Grants Committee
During aging, memory retention and persistence of long-term potentiation (LTP) are impaired, suggesting an aging-related deterioration in mechanisms regulating information storage. Late-phase LTP requires synthesis of proteins at synapses as well as integrated regulation of gene networks. Because aging diminishes the persistence of LTP, primarily by affecting the transition between early and late phases, we assessed whether this was reflected in perturbation of gene networks. Using DNA microarray analysis, we compared LTP-associated gene expression in young (5 months), middle-aged (15 months), and old (22 months) male Sprague-Dawley rats. As expected, we found no significant difference in LTP measured 20 minutes postinduction; however, we found that overall more genes were regulated in the young group. Bioinformatics predicted not only dysregulation of activator protein-1 and nuclear factor kappa B transcription factor activity and epigenetic modifications but also dysregulation of protein synthesis. Notably, we confirmed an age-related impairment in metabotropic and ionotropic receptor-mediated synaptic protein synthesis. Together, these results demonstrate that LTP-specific gene expression is altered with aging and suggest that dysregulation of synaptic protein synthesis also contributes to the age-dependent reduction in LTP persistence. (C) 2015 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据