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Positron emission tomographic evidence for progression of human MPTP-induced dopaminergic lesions
F J Vingerhoets1, B J Snow, J W Tetrud
1Department of Medicine, Vancouver Hospital, British Columbia, Canada.
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.
Insights
Transient exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes progressive parkinsonism. This toxin-induced condition shows a decline in brain function similar to idiopathic parkinsonism, suggesting environmental factors in neurodegeneration.
Area of Science:
- Neuroscience
- Toxicology
- Neurology
Background:
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure causes parkinsonism.
- The long-term progression of MPTP-induced parkinsonism is not well understood.
- Idiopathic parkinsonism (IP) is a progressive neurodegenerative disorder.
Purpose of the Study:
- To investigate the long-term effects of MPTP exposure on nigrostriatal dopaminergic function.
- To compare the progression of MPTP-induced parkinsonism with normal aging and IP.
- To assess the potential for transient toxin exposure to cause progressive neurodegeneration.
Main Methods:
- Longitudinal study involving 10 MPTP-exposed subjects and 10 controls.
- Fluorodopa positron emission tomography (FD-PET) scans performed 7 years apart.
- Clinical assessments of parkinsonism signs and symptoms.
Main Results:
- MPTP-exposed subjects showed a significant annual decline in FD-PET index (2.3% per year).
- The rate of decline in MPTP-exposed subjects was faster than normal aging.
- The progression rate in MPTP-exposed subjects was comparable to that observed in idiopathic parkinsonism.
Conclusions:
- Transient MPTP exposure leads to a progressive decline in nigrostriatal dopaminergic function.
- This decline is more rapid than normal aging and similar to IP progression.
- Findings support the hypothesis that environmental agents may trigger neurodegenerative disorders.