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- Title
Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure.
- Authors
Langston, J. W.; Forno, L. S.; Tetrud, J.; Reeves, A. G.; Kaplan, J. A.; Karluk, D.
- Abstract
This report provides the first detailed neuropathological study of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in humans. All 3 subjects self-administered the drug under the impression it was "synthetic heroin" and subsequently developed severe and unremitting parkinsonism, which was L-dopa responsive, at least in the earlier stages of illness. Survival times ranged from 3 to 16 years. Neuropathological examination revealed moderate to severe depletion of pigmented nerve cells in the substantia nigra in each case. Lewy bodies were not present. In Patients 1 and 2, there was gliosis and clustering of microglia around nerve cells. Patient 3 had a similar picture and also showed large amounts of extraneuronal melanin. These findings are indicative of active, ongoing nerve cell loss, suggesting that a time-limited insult to the nigrostriatal system can set in motion a self-perpetuating process of neurodegeneration. Although the mechanism by which this occurs is far from clear, the precedent set by the cases could have broad implications for human neurodegenerative disease.
- Publication
Annals of Neurology, 1999, Vol 46, Issue 4, p598
- ISSN
0364-5134
- Publication type
journal article
- DOI
10.1002/1531-8249(199910)46:4<598::AID-ANA7>3.0.CO;2-F