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Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine exposure
Author(s) -
Langston J. W.,
Forno L. S.,
Tetrud J.,
Reeves A. G.,
Kaplan J. A.,
Karluk D.
Publication year - 1999
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(199910)46:4<598::aid-ana7>3.0.co;2-f
Subject(s) - substantia nigra , parkinsonism , mptp , neurodegeneration , gliosis , medicine , pathology , neuroscience , microglia , parkinson's disease , disease , biology , inflammation
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.