A sheep model for MPTP induced Parkinson-like symptoms
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B D Hammock1, A M Beale, T Work
1Department of Entomology, University of California, Davis 95616.
Abstract:
Administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) causes behaviors reminiscent of idiopathic Parkinson's disease in man and other primates, but development of such symptomology has not been reported to date in other species. We now report a sheep model which responds to administration of low levels of the compound with well defined, apparently permanent symptomology very similar to that seen in primates. Histological examination indicates drug dependent destruction of the substantia nigra which, in sheep, lacks the high levels of neuromelanin present in primates. Following infusion of either MPTP or MPP+, only the metabolite MPP+ was detected in serum with this metabolite demonstrating a very long half life. The rapid disappearance of MPTP suggests that its potency will be directly related to a function of body size and inversely related to heart rate.
Insights
Researchers developed a sheep model for Parkinson's disease using MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Sheep exhibit permanent Parkinson's-like symptoms and substantia nigra destruction after MPTP administration.
Area of Science:
- Neuroscience
- Toxicology
- Animal Models
Background:
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces Parkinson's-like symptoms in primates.
- MPTP-induced Parkinsonism has not been reliably reproduced in other species.
Purpose of the Study:
- To establish a novel animal model for Parkinson's disease using sheep.
- To investigate the effects of MPTP in a non-primate species.
Main Methods:
- Administration of low levels of MPTP to sheep.
- Behavioral observation for Parkinson's-like symptoms.
- Histological examination of the substantia nigra.
- Pharmacokinetic analysis of MPTP and its metabolite MPP+.
Main Results:
- Sheep developed well-defined, permanent Parkinson's-like symptoms after MPTP exposure.
- Histology confirmed MPTP-induced destruction of the substantia nigra in sheep.
- The metabolite MPP+ had a long serum half-life, while MPTP rapidly disappeared.
- Sheep substantia nigra lacks high levels of neuromelanin found in primates.
Conclusions:
- Sheep represent a viable model for studying Parkinson's disease.
- MPTP-induced neurodegeneration in sheep mimics key aspects of human Parkinson's disease.
- Pharmacokinetics suggest MPTP potency is influenced by body size and heart rate.