Vaglini F, Pardini C, Cavalletti M, Maggio R, Corsini G U
Institute of Pharmacology, School of Medicine, University of Pisa, Italy.
Brain Res. 1996 Nov 25;741(1-2):68-74. doi: 10.1016/s0006-8993(96)00898-0.
L-Deprenyl, a monoamine oxidase (MAO)-B inhibitor, appears to slow down the progression of Parkinson's disease. While inhibition of MAO-B activity can account for some of the effects of this substance, the basis by which L-deprenyl slows the progression of the disease remains controversial. In recent years, a new mechanism of action has emerged that may explain the ability of L-deprenyl to increase neuronal survival. L-deprenyl has been reported to modify gene expression and protein synthesis in astrocytes and PC12 cells. In this study, we tested the ability of L-deprenyl to protect mouse mesencephalic cells from the toxicity of the 1-methyl-4-phenyl pyridinium ion (MPP+). We exposed mouse mesencephalic cell cultures to L-deprenyl (10 microM) and, 24 h later, to MPP+ (2.5 microM). On the fifth day after L-deprenyl and MPP+ exposition, cells were washed free of drugs, and the following day they were tested for dopamine uptake, intracellular dopamine content and tyrosine hydroxylase immunoreactivity. The experiments were performed either in the presence or in the absence of glia. It was found that L-deprenyl pretreatment failed to achieve any protection against MPP+ toxicity. The fall in dopamine uptake and intracellular dopamine content, and the diminution of tyrosine hydroxylase immunoreactivity observed in cells pretreated with L-deprenyl and then given MPP+ were not significantly different from the values observed in cells treated with MPP+ alone. Additional experiments performed in PC12 cells, confirmed the failure of L-deprenyl to abolish the toxicity of MPP+. Our data seem to be at variance with previous reports demonstrating that the MAO-B inhibitor L-deprenyl protects dopaminergic neurons against MPP+ toxicity [12,20]; furthermore they do not support alternative mechanisms of action of L-deprenyl against MPP+ toxicity.
L-司来吉兰是一种单胺氧化酶（MAO）-B抑制剂，似乎能减缓帕金森病的进展。虽然抑制MAO-B活性可以解释该物质的部分作用，但L-司来吉兰减缓疾病进展的基础仍存在争议。近年来，出现了一种新的作用机制，可能解释L-司来吉兰增加神经元存活的能力。据报道，L-司来吉兰可改变星形胶质细胞和PC12细胞中的基因表达和蛋白质合成。在本研究中，我们测试了L-司来吉兰保护小鼠中脑细胞免受1-甲基-4-苯基吡啶离子（MPP+）毒性影响的能力。我们将小鼠中脑细胞培养物暴露于L-司来吉兰（10微摩尔），24小时后再暴露于MPP+（2.5微摩尔）。在L-司来吉兰和MPP+暴露后的第五天，将细胞冲洗以去除药物，第二天测试它们的多巴胺摄取、细胞内多巴胺含量和酪氨酸羟化酶免疫反应性。实验在有或没有神经胶质细胞的情况下进行。结果发现，L-司来吉兰预处理未能对MPP+毒性起到任何保护作用。在用L-司来吉兰预处理然后给予MPP+的细胞中观察到的多巴胺摄取和细胞内多巴胺含量的下降，以及酪氨酸羟化酶免疫反应性的降低，与仅用MPP+处理的细胞中观察到的值没有显著差异。在PC12细胞中进行的额外实验证实，L-司来吉兰未能消除MPP+的毒性。我们的数据似乎与先前的报道不一致，先前的报道表明MAO-B抑制剂L-司来吉兰可保护多巴胺能神经元免受MPP+毒性影响[参考文献12,20]；此外，我们的数据也不支持L-司来吉兰针对MPP+毒性的其他作用机制。
