Abstract 180: Restoration of MiRNA MiR-181c-5p Rescue From the Detrimental Effect of Social Isolation in the Mice Subjected to Ischemic Stroke

Abstract

Introduction: MicroRNAs (miRNAs) are a class of short non-coding RNAs. Dysregulation of a variety of miRNAs have been tied to several neurological disorders including stroke. Recent studies have also found that microRNA profiles can change as a result of social environments. We have previously shown that the social isolation is detrimental to post-stroke recovery. MiR 181c-family of miRNA is one of the evolutionarily conserved and highly expressed miRNA family in the brain. Therefore, in this study we examined the specific role of miR-181c-5p after post-stroke social isolation. Methods: 2-3-month old C57BL/6 male mice were pair-housed (PH) for at least two weeks. After two weeks, a 60-minute right middle cerebral artery occlusion surgery (MCAO) was performed and mice were randomly assigned to one of two housing conditions, isolation or continued pair-housing (ST-ISO or ST-PH). In the treatment study group, ST-ISO mice were further randomly assigned to receive either miR-181c-5p mimic (7mg/kg i.v/day x drug) or a vehicle control administered through lateral tail vein at 24h and 48h after stroke. The effect of mimic treatment was evaluated at 1, 3, and 7 days after stroke using rotarod, open field test (OFT) and corner test. Mice were sacrificed 7 days after stroke for miRNA analysis. Results: Whole miRNone analysis of total RNA revealed miR 181-5p as one of the most affected miRNA in the brain tissue of post stroke socially isolated mice. Temporal profile expression data suggests that, miR-181c-5p was significantly down regulated (p<0.05 vs STPH) 7 days after stroke as compared to ST-PH controls. Treatment with miR-181c-5p mimic successfully increased miR-181c-5p miRNA expression in the treatment group as validated by qPCR analysis. Isolation-induced reduction in miR-181c-5p expression was rescued by mimic treatment. Post treatment with mimic reduced stroke mortality by 25% and partially restored motor deficit in post stroke socially isolated mice. Summary: The present data suggest that social isolation reduces miR-181c-5p after stroke. Restoration of this miRNA improved post stroke mortality and behavioral recovery. This microRNA is a valid target to reduce the detrimental effects of social isolation after ischemic stroke.