Annals of the New York Academy of Sciences 939:33-44 (2001)
© 2001 New York Academy of Sciences

Lack of Protective Effect by Intermittent Hypoxia on MPTP-Induced Neurotoxicity in Mice

GIN-HEUY LAIa, CHAU-FONG CHENb, YU SUc, LOW-TONE HOa AND ANYA MAAN-YUH LINa,c

In contrast to acute ischemia and subsequent reperfusion that produce excess free radicals, intermittent hypoxia (IH) is reported to play an important role in upregulation of antioxidative defensive mechanisms. In the study we report here, the neuroprotective effect of IH was evaluated using intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in ICR mice. Adult male ICR mice were subjected to 380 mmHg in an altitude chamber for 15 hours/day for 14 or 28 days. MPTP decreased striatal dopamine content in normoxic mice.

However, IH did not significantly alter the MPTP-induced depletion of striatal dopamine content. Furthermore, MPTP had no effect on GSH content but reduced GSH/GSSG ratio in mouse striatum. IH altered neither GSH content nor MPTP-induced reduction in GSH/GSSG ratio. Although MPTP had no effect on striatal SOD activity in normoxic mouse, IH increased SOD activity in the saline and MPTP groups. Neither MPTP nor IH affected GPx in mouse striatum.

Furthermore, in our ex vivo study, both the autooxidation and iron induced lipid peroxidation of cortical homogenates were lower in the IH-treated group than those of the normoxic group, indicating a reduced oxidative status after IH treatment.

In conclusion, exposure to IH has been suggested to be beneficial in preventing iron-induced oxidative injuries in biological organisms, and our data support this notion in that IH not only decreased iron-induced lipid peroxidation but also increased antioxidative defense enzyme activity in mouse brain.

Furthermore, the lack of neuroprotective effect by IH of MPTP-induced depletion of striatal dopamine content suggests that oxidative stress may not be the only mechanism for the MPTP-induced neurotoxicity.