MiR-181a regulates mitophagy and improves cognitive function in vascular dementia via targeting PINK1/Parkin pathway

Abstract

This study investigates the mechanism of miR-181a in cognitive function and mitophagy in vascular dementia. A rat model of vascular dementia was established by common carotid artery ligation and then divided into model group (n= 10), mimics group (n= 10), inhibitors group (n= 10), NC group (n= 10), and the remaining 10 rats were in sham operation group. The rats in mimics group were intravenously injected with miR-181a mimics and rats in inhibitors group were injected with miR-181a inhibitors. Model group and mimics group rats had a longer time on the 3rd to 4th day than sham operation group, and inhibitors group had a shorter time than model group and mimics group (allP<0.05). Time in quadrant of the cylindrical platform in model group and mimics group was shortened while it was prolonged in inhibitors group (P< 0.05). miR-181a mRNA level in model group, inhibitors group and NC group was lower. On the contrary, PINK1 and Parkin level was higher. miR-181a mRNA level was higher in mimics group with lower levels of PINK1 and Parkin (P<0.05). miR-181a level in mimics group was significantly increased and PINK1 and Parkin mRNA was decreased. miR-181a mRNA level in inhibitors group decreased significantly, while PINK1 and Parkin mRNA was increased (P<0.05). Parkin expression in mimics group and NC group was reduced. Up-regulation of miR-181 (mimics group) can target and inhibit PINK1/Parkin mRNA, thereby inhibiting mitophagy. miR-181a downregulation in mitochondria can promote PINK1/Parkin expression, thereby activating mitophagy in rats with vascular dementia, alleviating mitochondrial dysfunction, and improving the cognitive ability of rats.