Molecular mechanism of microRNA-132 regulation of neuronal apoptosis in mice with Alzheimer′s disease
10.3760/cma.j.cn113661-20210126-00044
- VernacularTitle:微小RNA132参与阿尔茨海默病模型鼠神经元凋亡的机制研究
- Author:
Kunpeng ZHAO
1
;
Jing MA
1
;
Yuling LI
1
;
Weixia XIAO
1
;
Yufeng LI
1
Author Information
1. 新乡医学院第二附属医院 河南省精神卫生中心老年精神科 453002
- Publication Type:Journal Article
- Keywords:
Alzheimer disease;
Apoptosis;
Mice
- From:
Chinese Journal of Psychiatry
2021;54(6):455-460
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the molecular mechanism of miR-132 regulation of neuronal apoptosis in Alzheimer′s disease model mice (AD mice).Methods:The study started and ended from 2016.01 to 2021.03. The animals were divided into the AD transgenic model mice group (AD model mice group) and the littermate negative control mice group (litter negative mice group). The number of animals in each group in the subsequent experiment was three mouses. The levels of miR-132 in the cortex and hippocampus of the two groups were detected by quantitative PCR. The TUNNEL(terminal-deoxynucleotidyl transferase-mediated nick end labeling) method was used to detect neuronal apoptosis in the brain tissue of the two groups of mice. The expression levels of apoptosis-related proteins in brain tissue of two groups of mice were detected by immunoblotting. The dual-luciferase reporter system recognizes downstream target proteins that miRNA-132 directly regulated. The independent sample Student′s t-test was used to compare the two groups, and the difference was statistically significant with P<0.05. Results:Compared with the littermate-negative mice, the relative expression of miRNA-132 in the cortex and hippocampus of AD mice was significantly down-regulated ( P<0.01). The results of TUNNEL showed a significant increase in neuronal apoptosis in the brain of AD mice (relative number of apoptotic cells ( P<0.01). Western blot results showed that the relative expression of apoptosis-related proteins in the brain of AD mice was significantly increased ( P<0.05 or P<0.01). The dual-luciferase reporter system showed that miRNA-132 could directly interact with the downstream protein FOXO3a, and the luciferase activity of the AD model group was significantly reduced ( P<0.01). Conclusions:miRNA-132 reduction may disinhibit apoptosis-related proteins BAX and Caspase-3 by up-regulating FOXO3a expression to speed up neuronal apoptosis in AD mice.
