Effects of different schedules of MPTP administration on dopaminergic neurodegeneration in mice
Identifieur interne : 004442 ( Main/Exploration ); précédent : 004441; suivant : 004443Effects of different schedules of MPTP administration on dopaminergic neurodegeneration in mice
Auteurs : E. Bezard [France] ; S. Dovero [France] ; B. Bioulac [France] ; C. Gross [France]Source :
- Experimental neurology [ 0014-4886 ] ; 1997.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (administration & dosage), Administration schedule, Animal, Animals, Comparative study, Degeneration, Dopamine Agents (administration & dosage), Dopamine Agents (toxicity), Dopaminergic neuron, Drug Administration Schedule, MPTP Poisoning, Male, Mice, Mouse, Nerve Degeneration (pathology), Nerve Tissue Proteins (analysis), Neurons (enzymology), Neurons (pathology), Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (pathology), Parkinson disease, Pathogenesis, 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.
Affiliations:
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Le document en format XML
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<term>Animal</term>
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<term>Comparative study</term>
<term>Degeneration</term>
<term>Dopamine Agents (administration & dosage)</term>
<term>Dopamine Agents (toxicity)</term>
<term>Dopaminergic neuron</term>
<term>Drug Administration Schedule</term>
<term>MPTP Poisoning</term>
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<term>Mice</term>
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<term>Nerve Degeneration (pathology)</term>
<term>Nerve Tissue Proteins (analysis)</term>
<term>Neurons (enzymology)</term>
<term>Neurons (pathology)</term>
<term>Parkinson Disease, Secondary (chemically induced)</term>
<term>Parkinson Disease, Secondary (pathology)</term>
<term>Parkinson disease</term>
<term>Pathogenesis</term>
<term>Tyrosine 3-Monooxygenase (analysis)</term>
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<term>Dopamine Agents</term>
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<front><div type="abstract" xml:lang="en">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.</div>
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