The Effects of N-Metyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Administration to Maternal Mice on the Catecholamine System in the Brain of Postnatal Mice
It is well-known that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces a reduction in the number ofop aminergic neurons in the nigro-striatal system of primates and rodents.1–3 The molecular basis of the neurodegeneration by MPTP has been intensively studied and the toxicity was found to be asribed to its oxidative product, 1-methyl-4- phenylpyridinium ion (MPP+)4. The sensitivity of mice to MPTP is agedependent5; systemic administration of MPTP in young mature Bice could not induce a long-lasting reduction in the dopamine (DA) level. Recently in our laboratory, MPTP was found to be transported from the maternal mouse to the fetus through the placenta, for MPTP and MPP+ were detected in the brains of fetal mice.7 MPP+ was reported to destroy the dopaminergic cells cultured from the rat embryonic mesencephalon,8 but the in vivo effect of MPTP on animals in the fetal stage has never been reported.
KeywordsTyrosine Hydroxylase Fetal Brain Postnatal Mouse Tyrosine Hydroxylase Activity MPTP Administration
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- 3.R. S. Burns, C. C. Chiueh, P. M. Sanford, M. H. Ebert, D. M. Jacobowitz, and J. K. Irwin, A primate model of parkinsonism: Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-metyl-4-phenyl-1,2,3,6-tetraphydrophridine, Proc. Natl. Acad. Sci. USA 80:4546 (1983).PubMedCrossRefGoogle Scholar
- 4.K. Chiba, A. Trevor, and N. Castagnoli, Jr., Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase, Biochem. Biophys. Res. Commun., 120:574 (1984).Google Scholar
- 7.Y. Ohya, M. Naoi, N. Ochi, N. Mizutani, K. Watanabe, and T. Nagatsu, Uptake of N-methyl-4-phenyl-1,2,3,6-tetraphydropyridine (MTPT) and the N-methyl-4-phenylpyridiniumion (MPP+) into fetal mouse brain through the placenta, Neurosci. Lett., 105:221 (1989).Google Scholar
- 8.C. Mytilineon and G. Cohen, 1-Metyl-4-phenyl-1,2,3,6tetrahydropyridine destroys dopamine neurons in explants of rat embryo mesencephalon, Science 225: 529 (1984).Google Scholar
- 12.M. M. Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal. Biochem., 72:248 (1976).Google Scholar
- 14.R. A. Mayer, A. S. Walters, and R. E. Heikkila, l-Metyl-4-phenyl1,2,3,6-tetrahydropyridine(MPTP) administration to C57-black mice leads to parallel decrements in neostriatal dopamine content and tyrosine hydroxylase activity, Eur. J. Pharmacol.120:375 (1986).Google Scholar