MovDisordV3, Main, Curation, bibRecord, 004976

Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model

Identifieur interne : 004976 ( Main/Curation ); précédent : 004975; suivant : 004977

Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model

Auteurs : Donato A. Di Monte [États-Unis] ; Alison Mccormack [États-Unis, Suède] ; Giselle Petzinger [États-Unis] ; Ann Marie Janson [États-Unis, Suède] ; Maryka Quik [États-Unis] ; William J. Langston [États-Unis]

Source :

Movement Disorders [ 0885-3185 ] ; 2000-05.

RBID : ISTEX:D13248DD2462D4AB89728A6C73E0B4B654F8743A

Descripteurs français

Pascal (Inist)
- Animal, Dyskinésie, Enervation, Modèle animal, Parkinson maladie, Physiopathologie, Singe, Voie nigrostriatale.
Wicri :
- topic : Singe.

English descriptors

KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animal, Animal model, Animals, Antiparkinson Agents (toxicity), Brain Mapping, Corpus Striatum (drug effects), Corpus Striatum (pathology), Corpus Striatum (physiopathology), Denervation, Dopamine, Dopamine (metabolism), Dyskinesia, Dyskinesia, Drug-Induced (pathology), Dyskinesia, Drug-Induced (physiopathology), Dyskinesias, Levodopa, Levodopa (toxicity), MPTP, Monkey, Monkeys, Neurons (drug effects), Neurons (pathology), Neurons (physiology), Nigrostriatal pathway, Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (pathology), Parkinson Disease, Secondary (physiopathology), Parkinson disease, Parkinson's disease, Pathophysiology, Receptors, Dopamine (drug effects), Receptors, Dopamine (physiology), Saimiri, Substantia Nigra (drug effects), Substantia Nigra (pathology), Substantia Nigra (physiopathology).
MESH :
- chemical , drug effects : Receptors, Dopamine.
- chemical , metabolism : Dopamine.
- chemical , physiology : Receptors, Dopamine.
- chemical , toxicity : Antiparkinson Agents, Levodopa.
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- chemically induced : Parkinson Disease, Secondary.
- drug effects : Corpus Striatum, Neurons, Substantia Nigra.
- pathology : Corpus Striatum, Dyskinesia, Drug-Induced, Neurons, Parkinson Disease, Secondary, Substantia Nigra.
- physiology : Neurons.
- physiopathology : Corpus Striatum, Dyskinesia, Drug-Induced, Parkinson Disease, Secondary, Substantia Nigra.
- Animals, Brain Mapping, Denervation, Saimiri.

Abstract

Presynaptic denervation is likely to play an important role in the pathophysiology of dyskinesias that develop after levodopa administration to patients with Parkinson's disease. In this study, the thresholds of nigrostriatal damage necessary for the occurrence of parkinsonism and levodopa‐induced involuntary movements were compared in squirrel monkeys lesioned with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). Animals treated with a regimen of MPTP that caused parkinsonism displayed ≥95% striatal dopamine depletion, 90% reduction of striatal dopamine uptake sites, and 70% nigral neuronal loss. Levodopa administration ameliorated the parkinsonian signs of these monkeys but also induced dyskinesias. A separate group of animals was treated with a milder MPTP regimen that caused 60%–70% striatal dopamine depletion, a 50% decrease in dopamine transporter, and 40% loss of dopaminergic nigral neurons. While these monkeys displayed no behavioral signs of parkinsonism, they all became dyskinetic after levodopa administration. The priming effect of levodopa, that is, the recurrence of dyskinesias in animals previously exposed to the drug, was compared in severely versus mildly lesioned monkeys. When severely injured parkinsonian animals underwent a second cycle of levodopa treatment, they immediately and consistently developed involuntary movements. In contrast, the recurrence of dyskinesias in primed monkeys with a partial nigrostriatal lesion required several levodopa administrations and remained relatively sporadic. The data indicate that moderate nigrostriatal damage which does not induce clinical parkinsonism predisposes to levodopa‐induced dyskinesias. Once dyskinesias have been induced, the severity of denervation may enhance the sensitivity to subsequent levodopa exposures.

Url:

https://api.istex.fr/document/D13248DD2462D4AB89728A6C73E0B4B654F8743A/fulltext/pdf

DOI: 10.1002/1531-8257(200005)15:3<459::AID-MDS1006>3.0.CO;2-3

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ISTEX:D13248DD2462D4AB89728A6C73E0B4B654F8743A

Le document en format XML

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<term>Dyskinesia, Drug-Induced (physiopathology)</term>
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<term>Levodopa (toxicity)</term>
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<term>Parkinson disease</term>
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<term>Substantia Nigra</term>
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<front><div type="abstract" xml:lang="en">Presynaptic denervation is likely to play an important role in the pathophysiology of dyskinesias that develop after levodopa administration to patients with Parkinson's disease. In this study, the thresholds of nigrostriatal damage necessary for the occurrence of parkinsonism and levodopa‐induced involuntary movements were compared in squirrel monkeys lesioned with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). Animals treated with a regimen of MPTP that caused parkinsonism displayed ≥95% striatal dopamine depletion, 90% reduction of striatal dopamine uptake sites, and 70% nigral neuronal loss. Levodopa administration ameliorated the parkinsonian signs of these monkeys but also induced dyskinesias. A separate group of animals was treated with a milder MPTP regimen that caused 60%–70% striatal dopamine depletion, a 50% decrease in dopamine transporter, and 40% loss of dopaminergic nigral neurons. While these monkeys displayed no behavioral signs of parkinsonism, they all became dyskinetic after levodopa administration. The priming effect of levodopa, that is, the recurrence of dyskinesias in animals previously exposed to the drug, was compared in severely versus mildly lesioned monkeys. When severely injured parkinsonian animals underwent a second cycle of levodopa treatment, they immediately and consistently developed involuntary movements. In contrast, the recurrence of dyskinesias in primed monkeys with a partial nigrostriatal lesion required several levodopa administrations and remained relatively sporadic. The data indicate that moderate nigrostriatal damage which does not induce clinical parkinsonism predisposes to levodopa‐induced dyskinesias. Once dyskinesias have been induced, the severity of denervation may enhance the sensitivity to subsequent levodopa exposures.</div>
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<front><div type="abstract" xml:lang="en">Presynaptic denervation is likely to play an important role in the pathophysiology of dyskinesias that develop after levodopa administration to patients with Parkinson's disease. In this study, the thresholds of nigrostriatal damage necessary for the occurrence of parkinsonism and levodopa-induced involuntary movements were compared in squirrel monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Animals treated with a regimen of MPTP that caused parkinsonism displayed ≥95% striatal dopamine depletion, 90% reduction of striatal dopamine uptake sites, and 70% nigral neuronal loss. Levodopa administration ameliorated the parkinsonian signs of these monkeys but also induced dyskinesias. A separate group of animals was treated with a milder MPTP regimen that caused 60%-70% striatal dopamine depletion, a 50% decrease in dopamine transporter, and 40% loss of dopaminergic nigral neurons. While these monkeys displayed no behavioral signs of parkinsonism, they all became dyskinetic after levodopa administration. The priming effect of levodopa, that is, the recurrence of dyskinesias in animals previously exposed to the drug, was compared in severely versus mildly lesioned monkeys. When severely injured parkinsonian animals underwent a second cycle of levodopa treatment, they immediately and consistently developed involuntary movements. In contrast, the recurrence of dyskinesias in primed monkeys with a partial nigrostriatal lesion required several levodopa administrations and remained relatively sporadic. The data indicate that moderate nigrostriatal damage which does not induce clinical parkinsonism predisposes to levodopa-induced dyskinesias. Once dyskinesias have been induced, the severity of denervation may enhance the sensitivity to subsequent levodopa exposures.</div>
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<front><div type="abstract" xml:lang="en">Presynaptic denervation is likely to play an important role in the pathophysiology of dyskinesias that develop after levodopa administration to patients with Parkinson's disease. In this study, the thresholds of nigrostriatal damage necessary for the occurrence of parkinsonism and levodopa-induced involuntary movements were compared in squirrel monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Animals treated with a regimen of MPTP that caused parkinsonism displayed > or =95% striatal dopamine depletion, 90% reduction of striatal dopamine uptake sites, and 70% nigral neuronal loss. Levodopa administration ameliorated the parkinsonian signs of these monkeys but also induced dyskinesias. A separate group of animals was treated with a milder MPTP regimen that caused 60%-70% striatal dopamine depletion, a 50% decrease in dopamine transporter, and 40% loss of dopaminergic nigral neurons. While these monkeys displayed no behavioral signs of parkinsonism, they all became dyskinetic after levodopa administration. The priming effect of levodopa, that is, the recurrence of dyskinesias in animals previously exposed to the drug, was compared in severely versus mildly lesioned monkeys. When severely injured parkinsonian animals underwent a second cycle of levodopa treatment, they immediately and consistently developed involuntary movements. In contrast, the recurrence of dyskinesias in primed monkeys with a partial nigrostriatal lesion required several levodopa administrations and remained relatively sporadic. The data indicate that moderate nigrostriatal damage which does not induce clinical parkinsonism predisposes to levodopa-induced dyskinesias. Once dyskinesias have been induced, the severity of denervation may enhance the sensitivity to subsequent levodopa exposures.</div>
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	Movement Disorders (revue)
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Movement Disorders (revue)

Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model

Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model

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