Electroacupuncture alleviated brain damages through miR-191a-5p targeting neuronal calcium sensor 1 after ischemic stroke.
Rejuvenation Res. 2017 May 24. Epub 2017 May 24. PMID: 28537507
Electroacupuncture (EA) administration before or after cerebral ischemia has been shown to afford protection against ischemic injury. However, the underlying mechanism of EA-mediated protection is still unclear. Functional microRNAs (miRNAs) are believed to play important roles in neuroprotection and synaptic plasticity during and after ischemia. In a previous study, we identified 20 miRNAs that are expressed in the penumbra and are significantly changed after EA treatment. Here, we used bioinformatics analysis to predict the biological functions and gene-networks of these miRNAs. Consistent with our predictions, down-regulation of miR-191a-5p in primary neurons and in cortexes of rats increased cell viability, decreased apoptosis, reduced infarct volumes, and improved neurological scores; whereas up-regulation of miR-191a-5p exacerbated neuronal injury and partly reversed the neuroprotective effect of EA treatment after ischemia/repercussion injury. In silico analysis predicted that miR-191a-5p targets Neuronal calcium sensor 1 (NCS-1), brain-derived neurotrophic factor (BDNF) and growth associated protein 43 (GAP43), and using luciferase reporter assays, we confirmed that the NCS-1 3'UTR is targeted by miR-191a-5p. Furthermore, lentivirus-mediated overexpression of NCS-1 in primary neurons and in the cortexes of rats induced neuroprotection, while lentivirus-mediated knockdown had the opposite effect. Taken together, these data suggest that miRNAs participate in the response to EA treatment after cerebral ischemia and further imply that NCS-1 may constitute a miR-191a-5p target gene and a potential therapeutic target for neuroprotection.