Neuroprotective effect of microRNA-124 on dopaminergic neurons in Parkinson' s disease models

Abstract

Objective To investigate the neuroprotective effect of microRNA-124 on dopaminergic neurons in Parkinson's disease models and its inflammation-related regulation mechanism.Methods The inflammation cell models were prepared by microglial BV2 murine cells; real-time quantitative PCR (qRT-PCR) was performed to analyze the expressions of inflammation-related miRNAs,including miR-21,miR-124,miR-155,miR-146a,miR-181c and miR-221-3p.The C57BL/6 mouse models of Parkinson's disease were established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MTPT)intraperitoneal injection,and then,administration of miR-124 via tail vein injection was performed;immunohistochemistry was performed to observe the apoptosis of dopaminergic neurons (TH-staining)and the activation ofmicroglial cells (Iba1-staining) in the substantia nigra of animal models before and after treatment; additionally,Western blotting and qRT-PCR were performed to analyze the expressions of the apoptosis-related proteins (caspase-3 and caspase-8).Results As compared with other 5 miRNAs,miR-124 showed significantly higher expression in BV2 cells (P＜0.05),and presented higher down-regulation after the induction of inflammatory.As compared with those in the Parkinson's disease models,significantly increased TH-positive cells,decreased Iba1-positive cells and down-regulated expressions of caspase-3 and caspase-8 in the substantia nigra of animal models after miR-124 ministration were observed (P＜0.05).Conclusion MiR-124 can slow down the apoptosis of dopaminergic neurons though inhibiting the activation of microglial cells,and maybe it is the key molecule ofpathogenesis of Parkinson's disease. Key words: MicroRNA-124; Parkinson's disease; Dopaminergic neuron; Neuroprotection