title: Genetic vitamin E deficiency does not affect MPTP susceptibility in the mouse brain.
abstract: Oxidative stress is involved in the degeneration of the nigrostriatal dopaminergic system in Parkinson's disease (PD). Vitamin E (alpha-tocopherol) is a potent antioxidant in the cell membrane that can trap free radicals and prohibit lipid peroxidation. The retention and secretion of vitamin E are regulated by alpha-tocopherol transfer protein (TTP) in the brain and liver. Dysfunction of TTP results in systemic deficiency of vitamin E in humans and mice, and increased oxidative stress in mouse brain. In this study, we investigated the effect of vitamin E deficiency in PD development by generating an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD using TTP knockout (TTP-/-) mice. Vitamin E concentration in the brains of TTP+/- mice was half that in TTP+/+ mice, and in TTP-/- mice, was undetectable. MPTP treatment tended to decrease striatal dopamine, but the effect was comparable and not significant in any of the three genotypes. Furthermore, the extent of loss of dopaminergic cell bodies in the substantia nigra did not differ among the groups. One the other hand, oral administration of vitamin E resulted in the partial protection of striatal dopaminergic terminals against MPTP toxicity. Our results suggest that vitamin E does not play a major protective role in MPTP-induced nigrostriatal dopaminergic neurodegeneration in the brain.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yong-Ri
authors.initials: YR
authors.lastname: Ren
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Nishida
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshimi
authors.forename: Toru
authors.initials: T
authors.lastname: Yasuda
authors.forename: Kou-Ichi
authors.initials: K
authors.lastname: Jishage
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchihara
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Hideki
authors.initials: H
authors.lastname: Mochizuki
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D003342:Corpus Striatum / Q000378:metabolism; D004198:Disease Susceptibility; D018492:Dopamine Antagonists / Q000494:pharmacology; D005838:Genotype; D005978:Glutathione / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000139:chemically induced*; D013378:Substantia Nigra / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology; D014811:Vitamin E Deficiency / Q000235:genetics / Q000503:physiopathology*
chemical_list: D018492:Dopamine Antagonists; D009498:Neurotoxins; C000606290:SOD1 protein, human; D014810:Vitamin E; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005978:Glutathione