期刊
NEUROCHEMISTRY INTERNATIONAL
卷 78, 期 -, 页码 117-121出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2014.09.009
关键词
Aging; miR-21; PDCD4; PTEN; RECK; Traumatic brain injury
资金
- National Institute of Aging, University of Kansas Alzheimer's Disease Center and Steve Palermo Endowment
The present study investigated the possible role of miR-21, a miRNA that has known prosurvival function, in poor outcomes in the elderly following traumatic brain injury compared to adults. Controlled cortical impact injury was induced in adult (5-6 months) and aged (22-24 months) C57/BL6 mice. miR-21 and four of its targets (PDCD4, TIMP3, RECK, PTEN) were analyzed at 1, 3, 7 days post injury in samples of injured cortex using real-time PCR analysis. Basal miR-21 expression was higher in the aged brain than in the adult brain. In the adult brain, miR-21 expression increased in response to injury, with the maximum increase 24 hours after injury followed by a gradual decrease, returning to baseline 7 days post-injury. In contrast, in aged mice, miR21 showed no injury response, and expression of miR-21 target genes (PTEN, PDCD4, RECK, TIMP3) was up-regulated at all post injury time points, with a maximal increase at 24 hours post injury. Based on these results, we conclude that the diminished miR21 injury response in the aged brain leads to up-regulation of its targets, with the potential to contribute to the poor prognosis following TBI in aging brain. Therefore, strategies aimed at up-regulation of miR-21 and/or down regulation of its targets might be useful in improving outcomes in the elderly following TBI. (C) 2014 Elsevier Ltd. All rights reserved.
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