MPP+ induced substantia nigra degeneration is attenuated in nNOS knockout mice

被引:60
作者
Matthews, RT
Beal, MF
Fallon, J
Fedorchak, K
Huang, PL
Fishman, MC
Hyman, BT
机构
[1] HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA
[2] MASSACHUSETTS GEN HOSP, DEPT MED, CARDIOVASC RES CTR, CHARLESTOWN, MA 02138 USA
[3] HARVARD UNIV, SCH MED, CHARLESTOWN, MA 02138 USA
关键词
D O I
10.1006/nbdi.1997.0141
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 1997 Academic Press.
引用
收藏
页码:114 / 121
页数:8
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