Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure.
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.
Langston
J W
JW
The Parkinson's Institute, Sunnyvale, CA 94089-1605, USA.
Forno
L S
LS
Tetrud
J
J
Reeves
A G
AG
Kaplan
J A
JA
Karluk
D
D
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D000328:Adult; D016923:Cell Death; D006801:Humans; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology*; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine