Matthews R T, Beal M F, Fallon J, Fedorchak K, Huang P L, Fishman M C, Hyman B T
Neurochemistry Laboratory, Massachusetts General Hospital, Boston, USA.
Neurobiol Dis. 1997;4(2):114-21. doi: 10.1006/nbdi.1997.0141.
Recent studies showed that neuronal nitric oxide synthase (nNOS) plays a role in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. In the present study we examined the effects of striatal injection of 1-methyl-4-phenylpyridinium (MPP+) on substantia nigra degeneration in mutant mice lacking the nNOS gene or the endothelial nitric oxide synthase (eNOS) gene. Both striatal lesion volume and substantia nigra degeneration were significantly attenuated in the nNOS mutant mice but not in the eNOS mutant mice. The mice lacking nNOS showed a significant attenuation of MPP+(-) induced increases of 3-nitrotyrosine concentrations in the striatum. In a separate experiment administration of 7-nitroindazole for 48 h after MPP+ injections significantly attenuated substantia nigra degeneration in rats. Immunohistochemical studies showed apposition of nNOS-positive neuronal processes on tyrosine hydroxylase-positive neurons. These results provide further evidence that neuronally derived NO and peroxynitrite play a role in MPP+ neurotoxicity.
最近的研究表明，神经元型一氧化氮合酶（nNOS）在1-甲基-4-苯基-1,2,3,6-四氢吡啶神经毒性中起作用。在本研究中，我们研究了向纹状体注射1-甲基-4-苯基吡啶鎓（MPP+）对缺乏nNOS基因或内皮型一氧化氮合酶（eNOS）基因的突变小鼠黑质变性的影响。在nNOS突变小鼠中，纹状体损伤体积和黑质变性均显著减轻，但在eNOS突变小鼠中则不然。缺乏nNOS的小鼠纹状体中MPP+诱导的3-硝基酪氨酸浓度升高显著减轻。在另一项实验中，MPP+注射后给予7-硝基吲唑48小时可显著减轻大鼠黑质变性。免疫组织化学研究显示nNOS阳性神经元突起与酪氨酸羟化酶阳性神经元相邻。这些结果进一步证明神经元来源的一氧化氮和过氧亚硝酸盐在MPP+神经毒性中起作用。
