Down-regulation of mitogen-activated protein kinase phosphatase-1 expression alleviated depressive-like behaviors and hippocampal neuronal apoptosis in the chronic unpredictable mild stress rats
10.3760/cma.j.cn113661-20210830-00263
- VernacularTitle:下调丝裂原活化蛋白激酶磷酸酶-1表达可改善慢性不可预测性温和应激大鼠抑郁样行为及海马神经元凋亡
- Author:
Mengjun GENG
1
;
Laipeng FENG
;
Jingyang GU
;
Cong LIU
;
Huiying WANG
;
Yan LI
;
Xiaoli ZHANG
;
Liqin ZHAO
;
Qiujing SHAO
;
Changhong WANG
Author Information
1. 新乡医学院第二附属医院，新乡 453002
- Publication Type:Journal Article
- Keywords:
Depressive disorder;
Apoptosis;
Chronic unpredictable mild stress;
Mitogen-activated protein kinase phosphatase-1;
Hippocampal neuro
- From:
Chinese Journal of Psychiatry
2022;55(1):47-55
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of mitogen-activated protein kinase phosphatase-1 (MKP-1) on depressive-like behaviors and hippocampal neuron apoptosis in chronic unpredictable mild stress (CUMS) rats.Methods:A total of 36 Sprague-Dawley male rats were randomly divided into 4 groups using a random number table, including the control group( n=8), CUMS group( n=8), virus control group( n=10), and MKP-1 down-regulated group( n=10), with 8 rats in each group. Except for the control group, rats in other groups were stressed by CUMS model of depression. Rats in the virus control group and MKP-1 down-regulated group received adeno-associated virus injections in the hippocampal CA1 and CA3 regions before CUMS modeling. Sucrose preference test, forced swimming test, and open field test were used to observe the behavioral changes of rats. Western blotting was used to detect the protein expression of MKP-1, B-cell lymphoma-2 gene (Bcl-2) and B-cell lymphoma-2 gene-related X protein (Bax), in the hippocampus. TUNEL staining was utilized to observe the morphology of apoptotic cells in the hippocampus CA1 area. Repeated measures variance was used to analyze body weight and behaviors, while an independent sample t-test was used to analyze protein levels. Results:Compared with the control group, the body weight of rats in the CUMS group decreased ( F=44.664); the sucrose preference rate decreased ( F=14.978); the forced swimming immobility time increased ( F=8.436); the number of defecation in the open field test increased ( F=9.572); the relative expression level of MKP-1 and Bax/Bcl-2 also significantly increased ( t=4.415,3.410), P<0.05 for all; Compared with the virus control group, rats in the MKP-1 down-regulation group showed a higher sucrose preference rate ( F=11.922) and a shorter forced swimming immobility time ( F=12.868), furthermore, the activity distance ratio in the central area increased ( F=6.291), the number of uprights in the open field test increased ( F=14.372), and the relative expression levels of MKP-1 and Bax/Bcl-2 ( t=3.775,6.193) decreased, P<0.05 for all. The number of DNA fragments in the nucleus of the hippocampal CA1 region of the CUMS group was significantly more than that of the control group. In comparison, the number of DNA fragments in the nucleus of the MKP-1 down-regulated group was substantially less than that of the virus control group. Conclusion:Down-regulation of MKP-1 gene alleviated depressive-like behavior and hippocampal neuron apoptosis in CUMS rats.
