Positron emission tomographic evidence for progression of human MPTP-induced dopaminergic lesions

Details

Serval ID
serval:BIB_1D12F9FE5AAD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Positron emission tomographic evidence for progression of human MPTP-induced dopaminergic lesions
Journal
Annals of Neurology
Author(s)
Vingerhoets  F. J., Snow  B. J., Tetrud  J. W., Langston  J. W., Schulzer  M., Calne  D. B.
ISSN
0364-5134 (Print)
Publication state
Published
Issued date
11/1994
Volume
36
Number
5
Pages
765-70
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Nov
Abstract
Transient exposure to the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a syndrome resembling idiopathic parkinsonism (IP). While IP inevitably progresses, the long-term evolution of MPTP-parkinsonism is unknown. Fluorodopa positron emission tomography (FD-PET) is a reliable tool for assessing nigrostriatal dopaminergic function. We performed FD-PET and clinical assessments on two occasions, 7 years apart, on 10 human subjects exposed to MPTP (age at the first scan, 32.7 +/- 6.9 yr [mean +/- SD], and on 10 normal individuals (age, 53 +/- 16 yr). At the time of their first scan, 5 of the subjects exposed to MPTP were clinically normal and 5 had limited signs of parkinsonism; 5 had new clinical deficits 7 years later. In the subjects exposed to MPTP, the PET index [(striatal-occipital)/occipital ratio] dropped by 2.3% per year from 0.70 +/- 0.10 (mean +/- SD) to 0.58 +/- 0.10 (p < 0.001). This was significantly faster than normal aging (p < 0.01) and similar to the progression observed in IP (p = 0.06). The findings suggest that short-term exposure to MPTP leads to a protracted decline in nigrostriatal dopaminergic function more rapid than occurs in normal aging and similar to IP progression. This is the first evidence that transient exposure to a toxin can cause progressive nigral pathology. At present, the mechanism leading to this progression is unknown. Our findings support the hypothesis that some neurodegenerative disorders may result from transient exposure to an environmental agent.
Keywords
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/*adverse effects Adult Aged Aged, 80 and over Corpus Striatum/physiopathology/radionuclide imaging Dihydroxyphenylalanine/analogs & derivatives/diagnostic use Disease Progression Dopamine/*physiology Female Humans Male Middle Aged Parkinson Disease, Secondary/chemically induced/*physiopathology/*radionuclide imaging Substantia Nigra/physiopathology/radionuclide imaging Syndrome Tomography, Emission-Computed/methods
Pubmed
Web of science
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25/01/2008 12:49
Last modification date
20/08/2019 12:53
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