title: Neuroprotective effects of stemazole in the MPTP-induced acute model of Parkinson's disease: Involvement of the dopamine system.
abstract: 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 (20mg/kg) four times at 2-h intervals for one day to induce Parkinsonism, and then treated with ST (10, 30 and 50mg/kg) or Madopar (120mg/kg) for 7days. 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 (∼24%, P<0.01) and DAT levels (∼26%, P<0.01) in MPTP mice treated with ST (50mg/kg) compared with the vehicle group. Madopar treatment showed weaker effects on TH-positive cells (∼21%, P<0.05) and DAT levels (∼21%, P<0.05). DA and its metabolite levels were significantly increased with ST (50mg/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.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, Department of Chemistry, Beijing Normal University, Beijing 100875, China.
authors.forename: Zhirui
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, Department of Chemistry, Beijing Normal University, Beijing 100875, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Xu
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, Department of Chemistry, Beijing Normal University, Beijing 100875, China.
authors.forename: Na
authors.initials: N
authors.lastname: Du
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, Department of Chemistry, Beijing Normal University, Beijing 100875, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Yale PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06516, USA.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, Department of Chemistry, Beijing Normal University, Beijing 100875, China. Electronic address: hanmei@bnu.edu.cn.
authors.forename: Mei
authors.initials: M
authors.lastname: Han
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004338:Drug Combinations; D006834:Hydrazines / Q000494:pharmacology* / Q000627:therapeutic use; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010069:Oxadiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000523:psychology; D013378:Substantia Nigra / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D004338:Drug Combinations; D006834:Hydrazines; D018696:Neuroprotective Agents; D010069:Oxadiazoles; C005177:benserazide, levodopa drug combination; C559095:hydrazinecarbothioamide,N-(4-(4,5-dihydro-5-thioxo-1,3,4-oxadiazol-2-yl)phenyl); D007980:Levodopa; D001545:Benserazide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Dopamine system; MPTP; Neuroprotection; Oxidative stress; Parkinson’s disease; Stemazole