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Assay System for Neurotoxicants Causing Parkinson’s Disease: 1-Methyl-4-Phenylpyridinium Ion (MPP+) Inhibits Survival of Cultured Neurons from Substantia Nigra of Fetal Monkey(Macaca fascicularis)

  • Yoichiro Kuroda
  • Kazuyo Muramoto
  • Kazuo Kobayashi
  • Yukio Hirata
  • Fumiaki Cho
  • Toshiharu Nagatsu
Part of the Advances in Behavioral Biology book series (ABBI, volume 38A)

Abstract

Most neurotoxicological research is carried out using living rodents (mice and rats). This has three main drawbacks. The first is the fundamental difficulty of extrapolating these results to human toxicity. However, obtaining statistical data on living non-human primates is practically impossible because of its high cost. The second is the killing of a great number of living animals in opposition to recent animal protection movements. The third is the difficulty of molecular and cellular studies in vivo. To avoid or decrease these scientific and social problems, it is worthwhile exploring the possibility of using in vitro preparations such as brain slices1 or cultured neurons2.

Keywords

Tyrosine Hydroxylase Substantia Nigra Dopaminergic Neuron Microtubule Associate Protein Human Toxicity 
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.

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References

  1. 1.
    Y. Kuroda, Brain slices, assay system for the neurotoxicity of environmental pollutants and drugs on mammalian central nervous system.in: Mechanisms of Toxicity and Hazard Evaluation”, Holmstedt et al. eds.,Elsevier, Amsterdam, pp 59–62 (1980).Google Scholar
  2. 2.
    Y. Kuroda, K. Inoue, K. Kobayashi and Y. Ohguchi, Detection of neurotoxicities by cultured cells, Seitai-Kagaku (Environmental Chemistry), 7: 47–55 (1984).Google Scholar
  3. 3.
    J.W. Langston, P. Ballard, J.W. Tetrud and I. Irwin, Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219: 979–980 (1983).PubMedCrossRefGoogle Scholar
  4. 4.
    R.S. Burns, C.C. Chiueh, S.P. Markey, M.H. Ebert, D.M. Jacobowitz and I.J. Kopin, A primate 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 (1983).PubMedCrossRefGoogle Scholar
  5. 5.
    T. Nagatsu and M. Yoshida, An endogenous substance of the brain, tetrahydroisoquinoline, produces parkinsonism in primates with decreased dopamine, tyrosine hydrooxylase and biopterin in the nigrostriatal regions. Neurosci. Lett. 87: 178–182 (1988).PubMedCrossRefGoogle Scholar
  6. 6.
    J.D. Houle and G.D. Das, Freezing of embryonic neural tissue and its transplantation in the rat brain, Brain Research 192: 570–574 (1980).PubMedCrossRefGoogle Scholar
  7. 7.
    K. Muramoto, K. Kobayashi, S. Nakanishi, Y. Matsuda and Y. Kuroda, Functional synapse formation between cultured neurons of rat cerebral cortex; block by a protein kinase inhibitor which does not permeate the cell membrane. Proc. Japan Acad. 64:Ser. B, 319–322 (1988).Google Scholar
  8. 8.
    I. Nagatsu, M. Sakai, M. Yoshida and T. Nagatsu, Aromatic L-amino acid decarboxylase-immunoreactive neurons in and around the cerebrospinal fluid-contacting neurons of the central canal do not contain dopamine or serotonin in the mouse and rat spinal cord. Brain Research, 475: 91–102 (1988).PubMedCrossRefGoogle Scholar
  9. 9.
    M. Naoi, T. Takahashi and T. Nagatsu, Effect of 1-methyl-4phenylpyridinium ion (MPP+) on catecholamine levels and activity of related enzymes in clonal rat pheochromocytoma PC-12h cells. Life Science 43: 1485–1491 (1988).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Yoichiro Kuroda
    • 1
  • Kazuyo Muramoto
    • 1
  • Kazuo Kobayashi
    • 1
  • Yukio Hirata
    • 2
  • Fumiaki Cho
    • 3
  • Toshiharu Nagatsu
    • 4
  1. 1.Department of NeurochemistryTokyo Metropolitan Institute for NeurosciencesTokyo 183Japan
  2. 2.Department of Anatomy, School of MedicineUniversity of the RyukyusOkinawaJapan
  3. 3.Tsukuba Primate Center for Medical ScienceNIHIbaraki 305Japan
  4. 4.Department of BiochemistryNagoya University School of MedicineNagoya 466Japan

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