γ-Tocopherol attenuates MPTP-induced dopamine loss more efficiently than α-tocopherol in mouse brain

Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse has been widely used as a rodent model of Parkinson's disease. In this study, α-tocopherol (αT) transfer protein knockout (heteromutant type, α-TTP(+/−)) mice were used to evaluate the protective effects of αT and γ-tocopherol (γT) against MPTP-induced neurotoxicity. The intraperitoneal administration of MPTP to mice induced a decrease in the striatal levels of dopamine (DA) 3 days after the administration in both α-TTP(+/−) and wild-type mice; these mice were fed an αT-deficient diet for 3 weeks before the MPTP administration. The DA levels in the α-TTP(+/−) mice, which had been fed a γT-fortified diet (0.10 wt.%) for 3 weeks and were administered with MPTP, were recovered to those of the control, whereas there was no significant protective effect of αT despite the considerably higher striatal concentration of αT than γT. The immunohistochemical study also revealed that γT exerted a protective effect against neurodegenerative toxicity of MPTP. Collectively, this is the first report showing that the protective effect of γT is stronger than that of αT against the MPTP-induced damage of dopaminergic neurons in the mouse.