Knock-down of ROCK2 gene improves cognitive function and reduces neuronal apoptosis in AD mice by promoting mitochondrial fusion and inhibiting its division.
- Author:
Minfang GUO
1
;
Huiyu ZHANG
1
;
Peijun ZHANG
1
;
Jingwen YU
1
;
Tao MENG
1
;
Suyao LI
2
;
Lijuan SONG
3
,
4
;
Zhi CHAI
2
;
Jiezhong YU
5
,
6
;
Cungen MA
5
,
7
,
8
Author Information
1. Institute of Brain Science, Shanxi Datong University, Datong 037009, China.
2. The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong 030619, China.
3. The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong 030619
4. Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
5. Institute of Brain Science, Shanxi Datong University, Datong 037009
6. The Fourth People's Hospital of Datong, Datong 037008, China. *Corresponding authors, E-mail: sxdtyjz@qq.com.
7. The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong 030619
8. Department of Physiology, Shanxi Medical University, Taiyuan 030001, China. *Corresponding authors, E-mail: macungen@sxtcm.edu.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
Mice;
Alzheimer Disease/pathology*;
Amyloid beta-Peptides/metabolism*;
Amyloid beta-Protein Precursor;
Apoptosis/genetics*;
bcl-2-Associated X Protein;
Caspase 3;
Cognition;
Disease Models, Animal;
Mice, Inbred C57BL;
Mice, Transgenic;
Mitochondrial Dynamics/genetics*
- From:
Chinese Journal of Cellular and Molecular Immunology
2023;39(8):701-707
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of knocking down Rho-associated coiled-coil kinase (ROCK2) gene on the cognitive function of amyloid precursor protein/presenilin-1 (APP/PS1) double transgenic mice and its mechanism. Methods APP/PS1 double transgenic mice were randomly divided into AD model group (AD group), ROCK2 gene knock-down group (shROCK2 group), ROCK2 gene knock-down control group (shNCgroup), and wild-type C57BL/6 mice of the same age served as the wild-type control (WT group). Morris water maze and Y maze were employed to test the cognitive function of mice. Neuron morphology was detected by Nissl staining. Immunofluorescence histochemical staining was used to detect the expression of phosphorylated dynamin-related protein 1 (p-Drp1) and mitochondrial fusion 1 (Mfn1). Western blot analysis was used to detect the expression ROCK2, cleaved-caspase-3 (c-caspase-3), B-cell lymphoma 2 (Bcl2), Bcl2-related protein X (BAX), p-Drp1, mitochondrial fission 1 (Fis1), optic atrophy 1 (OPA1), Mfn1 and Mfn2. Results Compared with AD group mice, the expression of ROCK2 in shROCK2 group mice was significantly reduced; the cognitive function was significantly improved with the number of neurons in the hippocampal CA3 and DG areas increasing, and nissl bodies were deeply stained; the expression of c-caspase-3 and BAX was decreased, while the expression of Bcl2 was increased; the expression of mitochondrial division related proteins p-Drp1 and Fis1 were decreased, while the expression of mitochondrial fusion-related proteins OPA1, Mfn1 and Mfn2 were increased. Conclusion Knock-down of ROCK2 gene can significantly improve the cognitive function and inhibit the apoptosis of nerve cells of APP/PS1 mice. The mechanism may be related to promoting mitochondrial fusion and inhibiting its division.
