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, a-tocopherol (alpha T) transfer protein knockout (heteromutant type, alpha-TTP(+/-)) mice were used to evaluate the protective effects of UT and gamma-tocopherol (gamma T) 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 alpha-TTP(+/-) and wild-type mice; these mice were fed an alpha T-deficient diet for 3 weeks before the MPTP administration. The DA levels in the alpha-TTP(+/-) mice, which had been fed a gamma T 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 aT despite the considerably higher striatal concentration of aT than gamma T. The immunohistochemical study also revealed that gamma T exerted a protective effect against neurodegenerative toxicity of MPTP. Collectively, this is the first report showing that the protective effect of gamma T is stronger than that of aT against the MPTP-induced damage of dopaminergic neurons in the mouse. (c) 2006 Elsevier Ireland Ltd. All rights reserved.