Abstract
The cardinal neurochemical abnormality in Parkinson's disease is the decreased dopamine content in the striatum, resulting from the loss of dopaminergic neurons in the mesencephalon. Precise analysis of the dopaminergic neurons in the midbrain demonstrates, however, that this cell loss is not uniform. Some dopaminergic cell groups are more vulnerable than others. The degree of cell loss is severe in the substantia nigra pars compacta, intermediate in the ventral tegmental area and cell group A8, but nonexistent in the central gray substance. This heterogeneity provides a good paradigm for analyzing the factors implicated in this differential vulnerability. So far, the neurons that degenerate have been shown to contain neuromelanin, high amounts of iron, and no calbinding28K, and to be poorly protected against oxidative stress. By contrast, the neurons that survive in Parkinson's disease are free of neuromelanin, calbindinD28-positive, contain low amounts of iron, and are better protected against oxidative stress. The analysis of the pattern of cell loss in Parkinson's disease may thus bring new clues as to the mechanism of nerve cell death in Parkinson's disease.
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Hirsch E. C., Graybiel A. M., and Agid Y. (1988)Nature 334, 345–348.
Dexter D. T., Carter C. J., Wells F. R., Javoy-Agid F., Agid Y., Lees A., Jenner P., and Marsden C. D. (1989)J. Neurochem. 52, 381–389.
Marsden C. D. (1983)J. Neural. Trans. Suppl. 19, 121–141.
Mann D. M. A., and Yates P. O. (1983)Mech. Ageing Dev. 21, 193–203.
Kastner A., Hirsch E. C., Lejeune O., Javoy-Agid F., and Agid Y. (1992)J. Neurochem. 59, 1080–1089.
Ceballos I., Lafon M., Javoy-Agid F., Hirsch E., Nicole A., Sinet P. M., and Agid Y. (1990)Lancet 335i, 1035, 1036.
Zhang P., Anglade P., Hirsch E. C., Javoy-Agid F., and Agid Y. (1993)Neuroscience, in press.
Martilla R. J., Lorentz H., and Rinne U. K. (1988)J. Neurol. Sci. 86, 321–331.
Saggu H., Cooksey J., Dexter D., Wells F. R., Lees A., Jenner P., and Marsden C. D. (1989)J. Neurochem. 53, 692–697.
Przedborski S., Kostic V., Jacson-Lewis V., Carlson E., Epstein C. J., and Cadet J. L. (1992)J. Neurosci. 12, 1658–1667.
Damier P., Hirsch E., Javoy-Agid F., Zhang P. and Agid Y. (1993)Neuroscience 52, 1–6.
Earle K. M. (1968)J. Neuropathol. Exp. Neurol. 27, 1–14.
Dexter D. T., Wells F. R., Lees A. J., Agid F., Agid Y., Jenner P., and Marsden C. D. (1989)J. Neurochem. 52, 1830–1836.
Sofic E., Paulus W., Jellinger K., Riederer P., and Youdim M. B. H. (1991)J. Neurochem. 56, 978–982.
Hirsch E. C., Brandel J. P., Galle P., Javoy-Agid F., and Agid Y. (1991)J. Neurochem. 56, 446–451.
Perl D. P., Good P. F., and Olanow C. W. (1993)Mt. Sinai J. Med. in press.
Jellinger K., Paulus W., and Grundke-Iqbal I. (1990)J. Neural Transm. 2, 327–340.
Jellinger K., Kienzl E., and Rumpelmayer G. (1992)J. Neurochem. 59, 1168–1171.
Youdim M. B. H., Ben-Shachar D., and Riederer P. (1990)J. Neural Trans. 32(Suppl.), 239–248.
Snider W. D. and Johnson E. M. (1989)Ann. Neurol. 26, 489–506.
Hyman C., Hofer M., Barde Y. A., Juhasz M., Yancopoulos G. D., Squinto S. P., and Lindsay R. M. (1991)Nature 350, 230–232.
Villares J., Faucheux B., Strada O., Hirsch E. C., Agid Y., and Javoy-Agid F. (1993)Brain Res. 19, 72–76.
Farber J. L., Chien K. R., and Mittnacht S. Jr. (1991)Am. J. Pathol. 102, 271–281.
Rothman S. M., and Olney J. W. (1987)TINS 10, 299–302.
Mayer M. L. and Westbrook G. L. (1987)TINS 10, 59–61.
Mattson M. P., Rychlik B., Chu C., and Christakos S. (1991)Neuron 6, 41–51.
Hirsch E. C., Mouatt A., Thomasset M., Javoy-Agid F., Agid Y., and Graybiel A. M. (1992)Neurodegeneration 1, 83–93.
Lavoie B., and Parent A. (1991)Soc. Neurosci. Abstr. 17, 143.
Manaye K. F., Sonsalla P. K., Brooks B. A., and German D. C. (1991)Soc. Neurosci. Abstr. 17, 1275.
Bean A. J., Elde R., Cao Y., Oellig C., Tamminga C., Goldstein M., Pettersson R. F., and Hokfelt T. (1991)Proc. Natl. Acad. Sci. USA 88, 10,237–10,241.
Casper D., Mytilineou C., and Blum M. (1991)J. Neurosci. Res. 30, 372–381.
Claude P., Parada I. M., Gordon K. A., D'Amore P. A., and Wagner J. A. (1988)Neuron 1, 783–790.
Date I., Notter M. F. D., Felten S. Y., and Felten D. L. (1990)Brain Res. 526, 156–160.
Fallon J. H., Serrogy K. B., Loughlin S. E., Morrison R. S., Bradshaw R. A., Knauer D. J., and Cunningham D. D. (1984)Science 224, 1107–1109.
Ferrari G., Minozzi M.-C., and Toffano G. (1989)Dev. Biol. 133, 140–147.
Goodman R., Slater E., and Herschman H. R. (1980)J. Cell Biol. 84, 495–500.
Hadjiconstantinou M., Fitkin J. G., Dali A., and Neff N. H. (1991)J. Neurochem. 57, 479–482.
Hofer M. M., and Barde Y. A. (1988)Nature 331, 261–265.
Knüssel B., Michel P. P., Schwaber J. S., and Hefti F. (1990)J. Neurosci. 10, 558–570.
Lewis E. J., and Chikaraishi D. M. (1987)Mol. Cell Biol. 7, 3332–3336.
Loy R., Heyer D., and DiStefano P. (1988)Soc. Neurosci. Abstr. 14, 302.
Matsuda S., Saito H., and Nishiyama N. (1990)Brain Res. 529, 310–316.
Otto D., and Unsicker K. (1990)J. Neurosci. 10, 1912–1921.
Park T. M., and Mytilineou C. (1991)Brain Res. 599, 83–97.
Rydel R. E., and Greene L. A. (1987)J. Neurosci. 7, 3639–3653.
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Hirsch, E.C. Biochemistry of Parkinson's disease with special reference to the dopaminergic systems. Mol Neurobiol 9, 135–142 (1994). https://doi.org/10.1007/BF02816113
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DOI: https://doi.org/10.1007/BF02816113