关键词:

microRNA?9?5p, 阿尔茨海默病, 小鼠, Tau 磷酸化

Abstract:

Objective To investigate the expression of microRNA⁃9⁃5p（miR⁃9⁃5p）in the hippocampus and plasma of a mouse model of Alzheimer′s disease（AD），and the effect of its overexpression on Tau pathology. Methods Male APPswe/PS1dE9（APP/PS1）transgenic mice and WT C57BL/6（WT）mice were selected as research subjects，and then they were randomly divided into 3 groups：Lv⁃WT group，Lv⁃con group and Lv⁃miR⁃ 9⁃5p group，with 18 mice in each group. Lv⁃miR⁃9⁃5p（4 × 105 TU）or Lv⁃con（4 × 105 TU）was slowly injected into bilateral hippocampus of the mice in the Lv⁃miR⁃9⁃5p group and Lv⁃con group. The behavior tests or electro⁃ physiology experiments were performed 30 days after the injection. miRNA expression and AT8 protein expression were analyzed by microarray and quantitative real⁃time PCR and immunoblotting and immunofluorescence，respec⁃ tively. Results Compared with the Lv⁃con group，the discrimination index，contextual fear cessation，cue condi⁃ tioned fear cessation，cross⁃platform times and target quadrant time were significantly increased（P < 0.05），and cross ⁃ platform time was significantly decreased in the Lv ⁃miR ⁃ 9⁃5p group（P < 0.05）. The density of synaptic spines and the percentage of mushroom spines in the hippocampus of mice in the Lv⁃miR⁃9⁃5p group were signifi⁃ cantly higher than those in the Lv⁃con group（P < 0.05），and the mice in the Lv⁃miR⁃9⁃5p group showed higher long⁃term enhancement. Compared with the Lv⁃WT group，the level of AT8 and the co⁃localization amount of AT8 and γH2AX in the hippocampus of mice in the Lv⁃con group were significantly increased（P < 0.05）. The amount of AT8 in the Lv⁃miR⁃9⁃5p group was significantly reduced than that in the Lv⁃con group（P < 0.05）. Conclusion miR⁃9⁃5p plays a beneficial role in AD pathogenesis by reducing aberrant Tau phosphorylation and DNA damage. 

Key words:

microRNA?9?5p, Alzheimer′s disease, mice, Tau phosphorylation