Expression of Fos in MPTP-Treated Mouse Brain

  • Katsunori Nishi
Part of the Advances in Behavioral Biology book series (ABBI, volume 47)


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.


Glial Fibrillary Acidic Protein Dopaminergic Neuron Locus Coeruleus Guanidinium Thiocyanate MPTP Administration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 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
  2. Ceccatelli, S., Villar, M.J., Goldstein, M. and Hokfelt, T., Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress, 1989, Proc. Natl. Acad. Sci. USA., 86: 9569–9573.PubMedCrossRefGoogle Scholar
  3. Chiba, K., Trevor, A.J., Castagnoli, N. Jr, 1985, Active uptake of MPP+, a metabolite of MPTP, by brain synaptosomes, Biochem. Biophys. Res. Commun., 120: 574–578.CrossRefGoogle Scholar
  4. Chomczynski, P. and Sacchi, N., 1987, Single step method of RNA isolation by acid guanidinium thiocyanatephenol-chloroform extraction, Anal. Biochem., 162: 156–159, 1987.PubMedCrossRefGoogle Scholar
  5. 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
  6. Dragnow, M., Butterworth, N., Waldvogel, H., Faull, R.L.M., Nicholson, L.F.B., 1995, Prolonged expression of Fos-related antigens, Jun B and TrkB in dopamine-denervated striatal neurons. Mol. Brain Res, 30: 393–396.CrossRefGoogle Scholar
  7. Duchemin, A. M., Gudehithlu, K.P., Neff, N.H., and Hadjiconstantinou, M., 1992, C-fos mRNAin mouse brain after MPTP treatment, Neurochem. Int. 20:281–287.PubMedCrossRefGoogle Scholar
  8. Gass, P., Herdegen, T., Bravo, R. and Kiessling, M., 1993, Induction and suppression of immediate early genes in specific rat brain regions by the non-competitive N-methyl-D-aspartate receptor antagonist MK-801, Neuroscience, 53: 749–758.PubMedCrossRefGoogle Scholar
  9. Heikkila, R.E., Hess, A., and Duvoisin, R.C., 1984, Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice, Science, 224:1451–1453.PubMedCrossRefGoogle Scholar
  10. Hisanaga K, Sagar, S.M. and Sharp, F.R., 1992, N-methyl-D-aspartate antagonists block Fos-like protein expression induced via multiple signaling pathways in cultured cortical neurons, J. Neurochem. 58: 1836–1844.PubMedCrossRefGoogle Scholar
  11. 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
  12. Langston, J.W., Bullard, P., Tetrud, J.W., and Irwin I., 1983, Chronic parkinsonism in humans due to a product of meperidine analog synthesis, Science, 219: 979–980.PubMedCrossRefGoogle Scholar
  13. Mizuno, Y., Sone, N. and Saitoh, T., 1987, Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenyl-pyridinium ion on activities of enzymes in the electron transport system in mouse brain. J. Neurochem. 48: 1787–1793.PubMedCrossRefGoogle Scholar
  14. Morgan, J.I. and Curran, T., 1991, Stimulus transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun, Annu. Rev. Neurosci. 14: 421–451.CrossRefGoogle Scholar
  15. Nicklas, W.J., Vyas I. and Heikkila, R.E., 1985, Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenylpyridine, a metabolite of neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahy-dropyridine, Life. Sci. 36: 2503–2508.PubMedCrossRefGoogle Scholar
  16. Ramsay, R.R., Salach, J.I., Dadgar, J., Singer, T.P., 1986, Inhibition of mitochondrial NADH dehydrogenase by pyridine derivatives and its possible relation to experimental and idiopathic parkinsonism, Biochem. Biophys. Res. Commun., 135: 269–275.PubMedCrossRefGoogle Scholar
  17. Senba, E., Matsunaga, K., Tohyama, M. and Noguchi, K., 1993, Stress-induced c-fos expression in the rat brain: activation mechanism of sympathetic pathway, Brain Res. Bull., 31: 329–344PubMedCrossRefGoogle Scholar
  18. 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
  19. Turski, L., Bressler, K., Rettig, K-J., Loschmann, P-A and Wachtel, H., 1991, Protection of substantia nigra from MPP+neurotoxicity by N-methyl-D-asparatate antagonists, Nature, 349: 414–418.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Katsunori Nishi
    • 1
  1. 1.Department of NeurologyTokyo Metropolitan Institute for NeuroscienceFuchu-shi Tokyo 183Japan

Personalised recommendations