Effects of different schedules of MPTP administration on dopaminergic neurodegeneration in mice.
Identifieur interne : 001462 ( PubMed/Curation ); précédent : 001461; suivant : 001463Effects of different schedules of MPTP administration on dopaminergic neurodegeneration in mice.
Auteurs : E. Bezard [France] ; S. Dovero ; B. Bioulac ; C. GrossSource :
- Experimental neurology [ 0014-4886 ] ; 1997.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (administration & dosage), Animals, Dopamine Agents (administration & dosage), Dopamine Agents (toxicity), Drug Administration Schedule, MPTP Poisoning, Male, Mice, Nerve Degeneration (pathology), Nerve Tissue Proteins (analysis), Neurons (enzymology), Neurons (pathology), Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (pathology), Tyrosine 3-Monooxygenase (analysis).
- MESH :
- chemical , administration & dosage : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Dopamine Agents.
- chemical , analysis : Nerve Tissue Proteins, Tyrosine 3-Monooxygenase.
- chemical , toxicity : Dopamine Agents.
- chemically induced : Parkinson Disease, Secondary.
- enzymology : Neurons.
- pathology : Nerve Degeneration, Neurons, Parkinson Disease, Secondary.
- Animals, Drug Administration Schedule, MPTP Poisoning, Male, Mice.
Abstract
Although a valuable 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of human Parkinson's disease has been developed, our knowledge of the course of nigral degeneration remains fragmentary. Experimental factors which could possibly influence the destructive process must be taken into account. To evaluate the impact of experimental design, we compared the effects of different schedules of injection of the same cumulative dose of MPTP, in mice, by measuring tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta. Massive injection of the total dose over 1 day (4 injections of 20 mg/kg) destroyed more dopaminergic neurons than did the long-term daily injections of a lower dose of MPTP (20 injections of 4 mg/kg). This suggests that different schedules of administration of MPTP might induce different mechanisms of neuronal death. These mechanisms need to be better understood if chronic models of intoxication that replicate the evolution of human Parkinson's disease more precisely are to be developed.
DOI: 10.1006/exnr.1997.6648
PubMed: 9398471
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Experimental factors which could possibly influence the destructive process must be taken into account. To evaluate the impact of experimental design, we compared the effects of different schedules of injection of the same cumulative dose of MPTP, in mice, by measuring tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta. Massive injection of the total dose over 1 day (4 injections of 20 mg/kg) destroyed more dopaminergic neurons than did the long-term daily injections of a lower dose of MPTP (20 injections of 4 mg/kg). This suggests that different schedules of administration of MPTP might induce different mechanisms of neuronal death. 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