Abstract
Vascular cognitive impairment (VCI) is the most common type of dementia after Alzheimer's disease (AD). Effective treatments for VCI are currently lacking. MicroRNA (miR)- 140-5p is associated with cerebral ischemia and poststroke depression, but its relationship with VCI remains unknown. A VCI model was established by bilateral common carotid artery occlusion (BCCAO) for 17 min in mice. Neurogenesis was evaluated by immunostaining for Nestin/bromodeoxyuridine (BrdU), NeuN/BrdU, and doublecortin (DCX)/BrdU. Neuroplasticity was assessed by quantifying synapsin-I and postsynaptic density protein 95 (PSD-95) protein levels. Predicted target genes were screened and verified using the dual luciferase reporter gene system. MiR-140-5p was upregulated in the hippocampus of the BCCAO mice 2 weeks following ischemia. Compared with control groups, the AAV-miR-140-5p group exhibited poorer cognitive performance alongside lower numbers of DCX/BrdU and NeuN/BrdU and less synapsin-I and PSD-95 in the dentate gyrus (P < 0.05). MiR-140-5p overexpression decreased the predicted target gene Prox1. Dual luciferase reporter system confirmed that Prox1 was a direct target site for miR-140-5p. In conclusion, our results suggest that miR-140-5p inhibits neurogenesis and neuroplasticity via downregulation of Prox1 and aggravates VCI. Our findings highlight that miR-140-5p is involved in the pathological process of VCI and provides information for the development of new treatments, which may need further inhibition tests to verify.