title: 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.
authors.affiliation: Department of Anatomy & Cell Biology, Kansas University Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
authors.affiliation: Department of Anatomy & Cell Biology, Kansas University Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Gregory
authors.affiliation: Department of Anatomy & Cell Biology, Kansas University Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA. Electronic address: nberman@kumc.edu.
authors.forename: Nancy E J
authors.initials: NE
authors.lastname: Berman
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis*
chemical_list: C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs
keywords: Aging; PDCD4; PTEN; RECK; Traumatic brain injury; miR-21