The protective effects of cordycepin on MPTP-induced dopaminergic neuron damage in mice and its mechanism
10.3969/j.issn.1001-1978.2018.06.012
- VernacularTitle:虫草素对MPTP诱导的小鼠多巴胺能神经元损伤的保护作用及其机制
- Author:
Yi-Yun FAN
1
;
Pei-Chen TANG
;
Xin-Xia GU
;
Xin ZHANG
;
Ying SUN
;
Bo-Cheng YU
;
Xiao-Yan ZHANG
;
Xiao-Qun GE
Author Information
1. 扬州大学医学院药理学教研室
- Keywords:
cordycepin;
MPTP;
Parkinson 's dis-ease;
apoptosis;
dopamine;
MAPK
- From:
Chinese Pharmacological Bulletin
2018;34(6):797-803
- CountryChina
- Language:Chinese
-
Abstract:
Aim To observe the protective effects of cordycepin ( Cor) on dopaminergic neurons in 1-meth-yl-4-phenyl-1 , 2 , 3 , 6-tetrahydropyridine ( MPTP )-in-duced mouse model of Parkinson's disease ( PD) and to explore its mechanism. Methods C57BL/6 mice were administered with MPTP to establish the PD mod-el. Mice in Cor groups were pretreated with Cor (2.5,5.0 and 10.0 mg·kg-1 ) by intragastric administra-tion, respectively. The motor functions of the mice were observed in the open-field test, rotarod test and pole test. The content of DA, the numbers of TH-im-munoreactive cells and apoptotic cells were measured respectively by HPLC-ECD, immunohistochemistry staining and TUNEL staining. The expression of apop-tosis related proteins and MAPK signaling pathway-re-lated proteins ( p38 , p-p38 , ERK1/2 , p-ERK1/2 JNK1/2 and p-JNK1/2 ) were determined by Western blot. Results Cor could significantly improve the mo-tor dysfunction in PD mice. The contents of DA, DOPAC and HVA in the striatum remarkably increased after administration of Cor in MPTP-induced mice. Mo-reover, Cor could obviously reduce both the loss of TH-immunoreactive neurons and the numbers of TUNEL-positive cells in substantia nigra pars compacta ( SNpc) of PD mice. The protein expressions of Bax and cleaved caspase-3 were markedly down-regulated,whereas those of Bcl-2 and the ration of Bcl-2/Bax were significantly up-regulated by Cor pre-treatment followed by MPTP treatment. Furthermore, the protein expressions of p-p38 , p-ERK1/2 and p-JNK1/2 signif-icantly decreased in substantia nigra in Cor groups. Conclusions The results suggest that Cor can protect DA neurons against MPTP-induced injury by inhibiting apoptosis, which may be closely relevant to the inhibi-tion of MAPK signaling pathways.
