| Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. | |
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MedLine Citation:
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PMID: 10514096 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J W Langston; L S Forno; J Tetrud; A G Reeves; J A Kaplan; D Karluk |
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Publication Detail:
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Type: Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Annals of neurology Volume: 46 ISSN: 0364-5134 ISO Abbreviation: Ann. Neurol. Publication Date: 1999 Oct |
Date Detail:
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Created Date: 1999-12-03 Completed Date: 1999-12-03 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7707449 Medline TA: Ann Neurol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 598-605 Citation Subset: IM |
Affiliation:
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The Parkinson's Institute, Sunnyvale, CA 94089-1605, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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adverse effects* Adult Cell Death Humans Male Nerve Degeneration / chemically induced*, pathology* Substantia Nigra / drug effects*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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R01 AG09121/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine |
| Comments/Corrections | |
Comment In:
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Ann Neurol. 2000 Jul;48(1):127
[PMID:
10894230
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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