Neuroprotective effects of stemazole in the MPTP-induced acute model of Parkinson's disease: Involvement of the dopamine system

摘要

Parkinson's disease is a neurodegenerative disorder characterized by a loss of nigrostriata dopaminergic neurons, which has been thought, at least in part, to result from oxidative stress. The present study aims to investigate the neuroprotective effects of stemazole (ST) on the dopamine (DA) system and its possible mechanisms of action in a mouse model of PD. Mice were injected intraperitoneally with MPTP (20 mg/kg) four times at 2-h intervals for one day to induce Parkinsonism, and then treated with ST (10, 30 and 50 mg/kg) or Madopar (120 mg/kg) for 7 days. Behavioral analyses were performed with locomotor activity measures and rotarod test. Tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels were detected by immunohistochemistry method. DA and its metabolites were determined by high-performance liquid chromatography with an electrochemical detector. Oxidative stress levels were assessed by measuring the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Our results demonstrated that ST treatment improved locomotor activity and motor coordination in MPTP mice. There was also a significant increase in TH-positive cells (similar to 24%, P<0.01) and DAT levels (similar to 26%, P<0.01) in MPTP mice treated with ST (50 mg/kg) compared with the vehicle group. Madopar treatment showed weaker effects on TH-positive cells (similar to 21%, P<0.05) and DAT levels (similar to 21%, P<0.05). DA and its metabolite levels were significantly increased with ST (50 mg/kg) treatment (P<0.01, compared with the vehicle group). In addition, SOD and GSH-PX activities were elevated notably in ST treatment groups compared with the vehicle group. In conclusion, these results suggest that ST has neuroprotective effect on the impaired DA system, potentially through enhancement of the cell's anti-oxidative capacity. Hence it may be used as a potential therapeutic agent for Parkinson's disease. (C) 2016 Elsevier Ireland Ltd. All rights reserved.