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Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease

Nature volume 334, pages 345–348 (1988)Cite this article

Abstract

In idiopathic Parkinson's disease massive cell death occurs in the dopamine-containing substantia nigra1,24. A link between the vulnerability of nigral neurons and the prominent pigmentation of the substantia nigra, though long suspected, has not been proved2. This possibility is supported by evidence that N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite MPP+, the latter of which causes destruction of nigral neurons, bind to neuromelanin3,4. We have directly tested this hypothesis by a quantitative analysis of neuromelanin-pigmented neurons in control and parkinsonian midbrains. The findings demonstrate first that the dopamine-containing cell groups of the normal human midbrain differ markedly from each other in the percentage of neuromelanin-pigmented neurons they contain. Second, the estimated cell loss in these cell groups in Parkinson's disease is directly correlated (r = 0.97, P = 0.0057) with the percentage of neuromelanin-pigmented neurons normally present in them. Third, within each cell group in the Parkinson's brains, there is greater relative sparing of non-pigmented than of neuromelanin-pigmented neurons. This evidence suggests a selective vulnerability of the neuromelanin-pigmented subpopulation of dopamine-containing mesencephalic neurons in Parkinson's disease.

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References

  1. Escourolle, R., De Recondo, J. & Gray, F. in Monoamines Noyaux gris cenlraux et syndromes de Parkinson (eds de Ajuriaguerra, J. & Gauthier, G.) 173–229 (Geneva, 1970).

    Google Scholar 

  2. Marsden, C. D. J. Neural Trans. Suppl. 19, 121–141 (1983).

    ADS  CAS  Google Scholar 

  3. D'Amato, R. J., Lipman, Z. P. & Snyder, S. H. Science 231, 987–989 (1986).

    ADS  CAS  Article  PubMed  Google Scholar 

  4. D'Amato, R. J. et al. Nature 327, 324–326 (1987).

    ADS  CAS  Article  PubMed  Google Scholar 

  5. Steele, J. C., Richardson, J. C. & Olszewski, J. Arch. Neurol. 10, 333–359 (1964).

    CAS  Article  PubMed  Google Scholar 

  6. Dahlström, A. & Fuxe, K. Acta physiol. scand. 62, (Suppl. 232) 1–55 (1964).

    Google Scholar 

  7. Garver, D. L. & Sladek, J. R. J. comp. Neurol. 159, 289–304 (1975).

    CAS  Article  PubMed  Google Scholar 

  8. Graybiel, A. M. & Ragsdale, C. W. Jr in Chemical Neuroanalomy (ed. Emson, P. C.) 427–504 (Raven, New York, 1983).

    Google Scholar 

  9. Lindvall, O. & Björklund, A. in Chemical Neuroanatomy (ed. Emson, P. C.) 229–255 (Raven, New York, 1983).

    Google Scholar 

  10. Graham, D. G. Molec. Pharmacol. 14, 633–643 (1978).

    CAS  Google Scholar 

  11. Lindquist, N. G. Acta radiol. Suppl. 325, 1–92 (1973).

    CAS  Google Scholar 

  12. Davis, G. C. et al. Psychiatry Res. 1, 249–256 (1979).

    ADS  CAS  Article  PubMed  Google Scholar 

  13. Langston, J. W., Ballard, P., Tetrad, J. W. & Irwin, I. Science 219, 979–980 (1983).

    ADS  CAS  Article  PubMed  Google Scholar 

  14. Burns, R. S. et al. Proc. natn. Acad. Sci. U.S.A. 80, 4546–4550 (1983).

    ADS  CAS  Article  Google Scholar 

  15. Mann, D. M. A. & Yates, P. O. Brain 97, 489–498 (1974).

    CAS  Article  PubMed  Google Scholar 

  16. Duvoisin, R. C. Clin. Neuropharmacol. 9, Suppl. 1 S3–S11 (1986).

    Article  PubMed  Google Scholar 

  17. Jimenez-Castellanos, J. & Graybiel, A. M. Neuroscience 23, 223–242 (1987).

    CAS  Article  PubMed  Google Scholar 

  18. Gerfen, C. R., Herkenham, M. & Thibault, J. J. Neurosci 7, 3915–3934 (1988).

    Article  Google Scholar 

  19. Deutch, A. Y. et al. Neurosci. Lelt. 68, 51–56 (1986).

    CAS  Article  Google Scholar 

  20. German, D. C., Dubach, M., Askari, S., Speciale, S. G. & Bowden, D. M. Neuroscience 24, 161–174 (1988).

    CAS  Article  PubMed  Google Scholar 

  21. Wilson, J. S., Turner, B. H., Morrow, G. D. & Hartman, P. J. Brain Res. 423, 329–332 (1987).

    CAS  Article  PubMed  Google Scholar 

  22. Hirsch, E. C., Graybiel, A. M., Duyckaerts, C. & Javoy-Agid, F. Proc. natn. Acad. Sci. U.S.A. 84, 5976–5980 (1987).

    ADS  CAS  Article  Google Scholar 

  23. Graybiel, A. M., Hirsch, E. C. & Agid, Y. A. Proc. natn. Acad. Sci. U.S.A. 84, 303–307 (1987).

    ADS  CAS  Article  Google Scholar 

  24. Jellinger, K. in Recent Developments in Parkinson's Disease (eds Fahn, S., Marsden, C. D., Jenner, P. & Teychenne, P.) 33–66 (Raven, New York, 1986).

    Google Scholar 

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Author information

Affiliations

  1. INSERM U289, Laboratoire de Medecine Experimentale, Hôpital de la Salpêtrière, 47 Bd. de I'Hôpital, 75013, Paris, France

    Etienne Hirsch & Yves A. Agid

  2. Department of Brain and Cognitive Sciences, Whitaker College, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    Ann M. Graybiel

  3. To whom correspondence should be addressed

    Ann M. Graybiel

Authors
  1. Etienne Hirsch
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  2. Ann M. Graybiel
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  3. Yves A. Agid
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Hirsch, E., Graybiel, A. & Agid, Y. Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature 334, 345–348 (1988). https://doi.org/10.1038/334345a0

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