Altered expression of miRNA-21 and its targets in the hippocampus after traumatic brain injury.

Traumatic brain injury (TBI) initiates many different signaling cascades throughout the brain that impact both pathophysiological and neuroprotective processes. Cellular mechanisms that can modulate these processes may play an important role in determining the nature and extent of the damage suffered after TBI and therefore influence overall outcome after injury. MicroRNAs (miRNAs) are an important class of noncoding regulatory RNAs providing an epigenetic mechanism for the regulation of protein expression levels of target genes. We report that miR-21 expression is significantly up-regulated in the hippocampus after rodent TBI, with expression levels peaking by 3 days postinjury and returning to near sham levels by 15 days postinjury. In situ localization of miR-21 transcripts indicates widespread expression in normal brain, with a pronounced increase in expression after TBI evident throughout the cortex and hippocampus, including the dentate gyrus and CA3 cell layer. We used a combination of the miRanda, TargetScan, and PicTar prediction algorithms to identify 99 potential target genes that possess miR-21 binding sites within their 3' untranslated regions. Analysis of these genes' annotated Gene Ontology molecular function and biological process terms revealed an overrepresentation of genes involved in enzyme-linked receptor signaling, transcriptional regulation, and developmental processes. These results suggest that increased miR-21 expression in the hippocampus may influence multiple components of TBI pathophysiology.