gamma-Tocopherol attenuates MPTP-induced dopamine loss more efficiently than alpha-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, alpha-tocopherol (alphaT) transfer protein knockout (heteromutant type, alpha-TTP((+/-))) mice were used to evaluate the protective effects of alphaT and gamma-tocopherol (gammaT) 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 alphaT-deficient diet for 3 weeks before the MPTP administration. The DA levels in the alpha-TTP((+/-)) mice, which had been fed a gammaT-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 alphaT despite the considerably higher striatal concentration of alphaT than gammaT. The immunohistochemical study also revealed that gammaT exerted a protective effect against neurodegenerative toxicity of MPTP. Collectively, this is the first report showing that the protective effect of gammaT is stronger than that of alphaT against the MPTP-induced damage of dopaminergic neurons in the mouse.
Itoh
Nanako
N
Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, AIST, 1-8-31 Midorigaoka Ikeda, Osaka 563-8577, Japan.
Masuo
Yoshinori
Y
Yoshida
Yasukazu
Y
Cynshi
Osamu
O
Jishage
Kou-ichi
K
Niki
Etsuo
E
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D014815:Vitamins / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology*; D024504:gamma-Tocopherol / Q000494:pharmacology*
D000975:Antioxidants; D014815:Vitamins; D024504:gamma-Tocopherol; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D024502:alpha-Tocopherol; D004298:Dopamine