Expression of Fos in MPTP-Treated Mouse Brain
One-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a selective neurotoxin of nigro-striatal dopaminergic neurons for primates (Burns et al., 1983) and human (Davis et al., 1979). It is known to cause severe and selective injury in nigro-striatal dopaminergic neurons in C57 black mice (Heikkila et al., 1984) and has been studied as a model of Parkinson’s disease. Previous studies revealed that MPTP is converted to 1-methyl-4-phenylpyridinium (MPP+) by monoamine oxidase(Chiba et al., 1985), selectively taken up by dopamine transporter and accumulate in dopaminergic neurons(Javitch et al., 1985). MPP+ is known to reduce complex I after entry into the dopaminergic terminal (Nicklas et al., 1985; Ramsay et al., 1986; Mizuno et al., 1987). As an alternative mechanism of neuronal injury, oxidative stress hypothesis has been advocated(Johannessen et al., 1985). Despite intensive studies, the precise mechanism by which the toxin causes degeneration of nigrostriatal dopaminergic neurons is not fully elucidated.
KeywordsGlial Fibrillary Acidic Protein Dopaminergic Neuron Locus Coeruleus Guanidinium Thiocyanate MPTP Administration
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- Burns, R.S., Chiueh, C. C., Markey, S.P., Ebert, M.H., Jacobowitz, D.M. and Kopin, I.J., 1983, Aprimate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Proc. Natl. Acad. Sci. USA, 80: 4546–4550.PubMedCrossRefGoogle Scholar
- Davis, G.C., Williams, A.C., Markey, S.P., Ebert, M.H., Caine, E.D., Reichert, C.M. and Kopin, I.J., 1979, Chronic parkinsonism secondary to intravenous injection of Meperidine analogues, Psychiatry Res, 1: 176–188.Google Scholar
- Javitch, J.A., D’Amato R.J., Strimatter, S.M., and Snyder, S.H., 1985, Parkinsonism-inducing neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity, Proc. Natl. Acad. Sci. U.S.A.,82: 2173–2177.PubMedCrossRefGoogle Scholar
- Sonsalla, P.K., Gail, D., Zeevalk, G.D., Manzino, L., Giovanni, A. and Nicklas, W.J., 1992, MK801 fails to protect against the dopaminergic neuropathology produced by systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice or intranigral 1-methyl-4-phenylpyridinium in rats, J. Neurochem. 58: 1979–1982.PubMedCrossRefGoogle Scholar