MicroRNA-125a-3p is involved in early behavioral disorders in stroke-afflicted rats through the regulation of Cadm2.

Abstract

Ischemic strokes carry a significant risk of mortality and recurrent vascular events. Recent studies suggest that changes in microRNAs (miRNAs or miRs) may affect the development of the stroke. However, few studies have investigated the role of miRNAs in behavioral disorder in early stroke. In the present study, animal models of middle cerebral artery occlusion (MCAO) are used, as well as a cell model of neurite outgrowth to further investigate the role of miRNAs in targeting synapse-associated proteins expression in early stroke. The authors used miRNA expression microarrays on RNA extracted from the cortex tissue samples from the rats of MCAO and control rats. Reverse transcription-quantitative polymerase chain reaction was conducted to verify the candidate miRNAs discovered by microarray analysis. Data indicated that miR-125a was significantly increased in the cortex of the model of MCAO, which were concomitant with that rats of MCAO at the same age displayed significant behavioral deficits. Bioinformatics analysis predicted the cell adhesion molecule 2 (Cadm2, mRNA) neurite outgrowth-associated protein is targeted by miR-125a. Overexpression of miR-125a reduced the level of Cadm2 expression in PC12 cell injury induced by free-serum. In contrast, inhibition of miR-125a using miR-125a inhibitors significantly resulted in higher levels of Cadm2 expression. In conclusion, miR-125a is involved in the behavioral disorder of animal models of MCAO by regulation of Cadm2.