出 处:《Journal of Shanghai Second Medical University(Foreign Language Edition)》2002年第1期1-6,共6页上海第二医科大学学报(英文版)
基 金:SupportedbytheNationalProgramofBasicResearch (BrainScience ,G19990 5 40 0 8)ofChina ,thetrainingprogramfortheChineseMinistryofEducationspecialfortheReturnScholarsfromabroad ,andthe 10 0 Cross CenturyoutstandingscholarsofacademicscienceinShanghaiHea
摘 要:Objective To investigate the possible role of apoptosis in the pathogenesis of Parkinson’s disease. Methods C- 57 BL mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP), and TUNEL and flow cytometry were employed to detect neuronal apoptosis in the substantia nigra. Results The results of animal experiment demonstrated that the administration of MPTP 30mg/kg for 7d could induce neuronal apoptosis in the substantia nigra. The MPTP-induced nigral neuronal apoptosis could be completely prevented by pre-treatment of Eldepryl, an inhibitor of B typed monoamine oxidase (MAO-B);and partially protected by pre-treatment of Riluzole, an antagonist of excitatory amino acid receptors. Data of cell culture experiment showed that 20mmol 1-methyl-4-phenylpyridinium ion(MPP +) induced the apoptosis of pheochromocytoma(PC12 cells), whereas 20mmol MPTP did not cause PC12 cells apoptosis. Conclusion It is concluded that the apoptotic effect of MPTP in vivo on the nigral neurons may be mediated by its intermediate metabolite MPP +. The dopaminergic neuronal apoptosis in the substantia nigra may be a common pathway of various causes that lead to the onset of Parkinson’s disease.Objective To investigate the possible role of apoptosis in the pathogenesis of Parkinson's disease. Methods C- 57 BL mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP), and TUNEL and flow cytometry were employed to detect neuronal apoptosis in the substantia nigra. Results The results of animal experiment demonstrated that the administration of MPTP 30mg/kg for 7d could induce neuronal apoptosis in the substantia nigra. The MPTP-induced nigral neuronal apoptosis could be completely prevented by pre-treatment of Eldepryl, an inhibitor of B typed monoamine oxidase (MAO-B);and partially protected by pre-treatment of Riluzole, an antagonist of excitatory amino acid receptors. Data of cell culture experiment showed that 20mmol 1-methyl-4-phenylpyridinium ion(MPP +) induced the apoptosis of pheochromocytoma(PC12 cells), whereas 20mmol MPTP did not cause PC12 cells apoptosis. Conclusion It is concluded that the apoptotic effect of MPTP in vivo on the nigral neurons may be mediated by its intermediate metabolite MPP +. The dopaminergic neuronal apoptosis in the substantia nigra may be a common pathway of various causes that lead to the onset of Parkinson's disease.
关 键 词:Parkinson's disease apoptosis substantia nigra PC12 MPTP MPP + Eldepryl Riluzole
分 类 号:R742.5[医药卫生—神经病学与精神病学]
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