Chronic MPTP treatment reproduces in baboons the differential vulnerability of mesencephalic dopaminergic neurons observed in Parkinson's disease
| Autor: | M. Varastet, Mariannick Mazière, P. Hantraye, D. Riche |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
Parkinson's disease Tyrosine 3-Monooxygenase animal diseases Dopamine Substantia nigra Biology Midbrain chemistry.chemical_compound Mesencephalon Dopaminergic Cell Internal medicine medicine Animals Neurons Pars compacta General Neuroscience MPTP Dopaminergic MPTP Poisoning Parkinson Disease medicine.disease Immunohistochemistry nervous system diseases Ventral tegmental area Substantia Nigra Endocrinology medicine.anatomical_structure nervous system chemistry Neuroscience Papio |
| Zdroj: | Neuroscience. 63(1) |
| ISSN: | 0306-4522 |
| Popis: | Chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to baboons was shown previously to result in a motor syndrome and a pattern of striatal dopaminergic fibre loss similar to those observed in idiopathic Parkinson's disease. In the present study, tyrosine hydroxylase-immunoreactive neurons were quantified in the mesencephalon of control ( n = 4) and chronically MPTPtreated ( n = 3) baboons. MPTP induced a significant reduction in neuronal cell density in the substantia nigra (63.8% reduction) and the ventral tegmental area (53.1%). Within the substantia nigra, obvious mediolateral and dorsoventral gradients of neuronal cell loss were observed. First, the pars lateralis was more affected than the lateral divisions of the pars compacta (89.6% vs 73.8% cell loss), which in turn were more depleted than the medial divisions (60.1% reduction). Second, the ventral regions of the pars compacta were more degenerated than the dorsal parts (82.4 vs 51.5% decrease). This regional pattern is strikingly similar to that observed in Parkinson's disease and indicates that two subpopulations of dopaminergic neurons are distinguishable on the basis of their differential vulnerability to MPTP. Finally, the present study confirms that chronic mitochondrial complex I inhibition using MPTP in primates is sufficient to reproduce the typical dopaminergic cell loss and striatal fibre depletion observed in Parkinson's disease. |
| Databáze: | OpenAIRE |
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