Neuroprotective Effects of Low-molecular-weight Chondroitin Sulfate on Dopaminergic Neurons in MPTP-induced Parkinson ’s Disease Model Mice
- VernacularTitle:低分子量硫酸软骨素对MPTP致帕金森病模型小鼠多巴胺能神经元的保护作用
- Author:
Qin GAO
1
;
Hongguang DING
2
;
Fusheng SUN
3
;
Zhihong YANG
1
;
Jing WANG
1
;
Huiting DING
1
;
Hua GAO
1
;
Chuanxia JU
1
Author Information
1. School of Pharmacy，Qingdao University，Shandong Qingdao 266012，China
2. Dept. of General Surgery，Qingdao Municipal Hospital，Shandong Qingdao 266011，China
3. Dept. of Pharmacy，Qingdao Municipal Hospital，Shandong Qingd ao 266011，China
- Publication Type:Journal Article
- Keywords:
Low-molecular-weight chondroitin sulfate;
Substantia nigra;
Striatum;
Dopaminergic neurons;
1-methyl-4-phenyl- 1，2，3，6-tetrahydropyridine;
Tyrosine hydroxylase;
Oxidant stress;
Parkinson’s disease;
Mice
- From:
China Pharmacy
2019;30(8):1025-1030
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE： To observe neuroprotective effects of low-molecular-weight chondroitin sulfate （CS） on dopaminergic neurons in Parkinson’s disease （PD） mice model induced by 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）. METHODS： C57BL/6 mice were randomly divided into control group， MPTP injury group， low-molecular-weight CS low-dose and high-dose groups （100， 400 mg/kg）. Control group and MPTP injury group were given constant volume of normal saline intragstrically， administration groups were given relevant medicine intragastrically， once a day， for consecutive 17 d. Since 11th day after medication， except for control group， other groups were given MPTP solution （20 mg/kg） intraperitoneally to induce PD model， once a day， consecutive 5 d. After last medication， behavioral changes of mice （10 mice in each group） were evaluated by rotary rod fatigue tester. The damage of dopamine neurons （the percentage of TH positive cell and the percentage of fluorescence intensity） in substantia nigra of mice （3 mice in each group） was detected by immunohistochemistry and immunofluorescence. The content of dopamine in striatum was determined by HPLC （6 mice in each group）. The changes of oxidant stress indexes （SOD， GSH-Px， MDA） in substantia nigra of mice were determined by chemical colorimetry （6 mice in each group）. RESULTS： Compared with control group， retention time of mice on rotating rods was shortened significantly in MPTP injury group； TH positive cells of substantia nigra were decreased significantly， fluorescence intensity was obviously weakened； the percentage of positive cells and fluorescence intensity， the content of dopamine in striatum， the activities of SOD and GSH-Px in substantia nigra were decreased significantly， while the content of MDA was increased significantly （P＜0.01）. Compared with MPTP injury group， retention time of mice on the rotating rods was prolonged significantly in low-molecular-weight CS groups， the number of TH positive cells was increased significantly in substantia nigra and fluorescence intensity was increased significantly； the percentage of positive cells， the percentage of fluorescence intensity and the content of dopamine in striatum were increased significantly， while above indexes of high-dose group were significantly longer or higher than those of low-dose group （P＜0.05 or P＜0.01）. The activities of SOD and GSH-Px in substantia nigra were increased significantly in low-molecular-weight CS groups， while the content of MDA in substantia nigra was decreased significantly in low-molecular-weight CS high-dose group （P＜0.05 or P＜0.01）. CONCLUSIONS： Prophylactic administration of low-molecular-weight CS can relieve the damage of dopaminergic neurons in substantia nigra of PD model mice induced by MPTP in a dose-dependent manner， and increase the secretion of dopamine in striatum. The effect may be related to the inhibition of lipid peroxidation and the enhancement of antioxidant capacity of tissues.
