| Summary: | 碩士 === 國立陽明大學 === 生理學研究所 === 88 === In contrast to an acute ischemia and a subsequent re-oxygenation that produces excess free radicals, intermittent hypoxia (IH) is reportedly to play an important role in up-regulation of antioxidative defense systems. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective neurotoxin of nigrostriatal dopaminergic neurons has been shown to induce neurodegeneration. One of the possible mechanisms underlying MPTP-induced neurotoxicity is via oxidative stress. In the present study, the effect of IH on MPTP-induced neurotoxicity was investigated. Adult, male mice (ICR strain) were subjected to 380 mmHg in an altitude chamber for 15 hours/day for 7 days and 21 days. MPTP (30 mg/kg/d) or saline was administered intraperitoneally in IH or normoxia groups for the following 5 days. Our results showed that MPTP depleted striatal dopamine (DA) content in both normoxia and IH groups. Furthermore, IH slightly prevented MPTP-induced DA depletion in mouse striatum. Autoxidation and iron-induced lipid peroxidation of brain homogenates were decreased in the IH group. Striatal glutathione (GSH) content in IH mice was higher than that in normoxia group. Moreover, cortical GSH content in the IH mice was elevated. However, GSH content was not increased in the hippocampus of chronic hypoxia-treated mice. Superoxide dismutase (SOD), but not glutathione peroxidase activity was increased in the striatum of IH mice. Bcl-2 level was increased in the striatum of IH mice. Our study suggests that intermittent hypoxia slightly prevents MPTP-induced neurotoxicity in the nigrostriatal dopaminergic system of IRC mice. Furthermore, elevation in antioxidative defense systems, including increases in GSH, Bcl-2 and SOD activity in brain tissues may contribute to the protection by intermittent hypoxia of MPTP-induced neurotoxicity.
|
|---|
