Document Detail


Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure.
MedLine Citation:
PMID:  10514096     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
J W Langston; L S Forno; J Tetrud; A G Reeves; J A Kaplan; D Karluk
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Publication Detail:
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:
Title:  Annals of neurology     Volume:  46     ISSN:  0364-5134     ISO Abbreviation:  Ann. Neurol.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-12-03     Completed Date:  1999-12-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  598-605     Citation Subset:  IM    
Affiliation:
The Parkinson's Institute, Sunnyvale, CA 94089-1605, USA.
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MeSH Terms
Descriptor/Qualifier:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / adverse effects*
Adult
Cell Death
Humans
Male
Nerve Degeneration / chemically induced*,  pathology*
Substantia Nigra / drug effects*,  pathology
Grant Support
ID/Acronym/Agency:
R01 AG09121/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Comments/Corrections
Comment In:
Ann Neurol. 2000 Jul;48(1):127   [PMID:  10894230 ]

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