Differential response of miRNA-21 and its targets after traumatic brain injury in aging mice

Abstract 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.