MiR-9-5p inhibits mitochondrial damage and oxidative stress in AD cell models by targeting GSK-3β.

Abstract

This study aims to investigate the effects and underlying mechanisms of overexpression microRNA-9-5p (miR-9-5p) on the Aβ-induced mouse hippocampal neuron cell line HT22. Different concentrations of Aβ25-35 (10, 20, 40, 80, and 160μM) treatment were used to establish AD model in HT22 cells. The CCK-8 assay was used to measure the cell viability. The mRNA expression levels of miR-9-5p and glycogen synthase kinase-3β (GSK-3β) were determined by RT-qPCR. HT22 cell apoptosis was analyzed flow cytometry. MiR-9-5p was down-regulated in Aβ25-35-induced HT22 cells. GSK-3β is a functional target for miR-9-5p. MiR-9-5p overexpression inhibited Aβ25-35-induced mitochondrial dysfunction, cell apoptosis, and oxidative stress by regulating GSK-3β expression in HT22 cells. Furthermore, through targeting GSK-3β, overexpression of miR-9-5p partly activated nuclear factor Nrf2/Keap1 signaling, including part increases of Nrf2, HO-1, SOD-1, GCLC expression and slight decrease of Keap1 expression. Our results showed miR-9-5p may play a powerful role in the pathogenesis of AD.