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Genetic vitamin E deficiency does not affect MPTP susceptibility in the mouse brain
Author(s) -
Ren YongRi,
Nishida Yoichiro,
Yoshimi Kenji,
Yasuda Toru,
Jishage Kouichi,
Uchihara Toshiki,
Yokota Takanori,
Mizuno Yoshikuni,
Mochizuki Hideki
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03994.x
Subject(s) - mptp , substantia nigra , dopaminergic , endocrinology , medicine , oxidative stress , neurodegeneration , dopamine , vitamin e , nigrostriatal pathway , parkinson's disease , vitamin e deficiency , chemistry , biology , antioxidant , biochemistry , disease
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.