Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model.
Identifieur interne : 000268 ( Ncbi/Merge ); précédent : 000267; suivant : 000269Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model.
Auteurs : D A Di Monte [États-Unis] ; A. Mccormack ; G. Petzinger ; A M Janson ; M. Quik ; W J LangstonSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2000.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Antiparkinson Agents (toxicity), Brain Mapping, Corpus Striatum (drug effects), Corpus Striatum (pathology), Corpus Striatum (physiopathology), Denervation, Dopamine (metabolism), Dyskinesia, Drug-Induced (pathology), Dyskinesia, Drug-Induced (physiopathology), Levodopa (toxicity), Neurons (drug effects), Neurons (pathology), Neurons (physiology), Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (pathology), Parkinson Disease, Secondary (physiopathology), 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 > 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.
PubMed: 10830409
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Quik</name></author><author><name sortKey="Langston, W J" sort="Langston, W J" uniqKey="Langston W" first="W J" last="Langston">W J Langston</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="2000" type="published">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Animals</term><term>Antiparkinson Agents (toxicity)</term><term>Brain Mapping</term><term>Corpus Striatum (drug effects)</term><term>Corpus Striatum (pathology)</term><term>Corpus Striatum (physiopathology)</term><term>Denervation</term><term>Dopamine (metabolism)</term><term>Dyskinesia, Drug-Induced (pathology)</term><term>Dyskinesia, Drug-Induced (physiopathology)</term><term>Levodopa (toxicity)</term><term>Neurons (drug effects)</term><term>Neurons (pathology)</term><term>Neurons (physiology)</term><term>Parkinson Disease, Secondary (chemically induced)</term><term>Parkinson Disease, Secondary (pathology)</term><term>Parkinson Disease, Secondary (physiopathology)</term><term>Receptors, Dopamine (drug effects)</term><term>Receptors, Dopamine (physiology)</term><term>Saimiri</term><term>Substantia Nigra (drug effects)</term><term>Substantia Nigra (pathology)</term><term>Substantia Nigra (physiopathology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptors, Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Receptors, Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Corpus Striatum</term><term>Neurons</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Corpus Striatum</term><term>Dyskinesia, Drug-Induced</term><term>Neurons</term><term>Parkinson Disease, Secondary</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Corpus Striatum</term><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease, Secondary</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Brain Mapping</term><term>Denervation</term><term>Saimiri</term></keywords></textClass></profileDesc></teiHeader><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></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">10830409</PMID><DateCreated><Year>2000</Year><Month>10</Month><Day>02</Day></DateCreated><DateCompleted><Year>2000</Year><Month>10</Month><Day>02</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0885-3185</ISSN><JournalIssue CitedMedium="Print"><Volume>15</Volume><Issue>3</Issue><PubDate><Year>2000</Year><Month>May</Month></PubDate></JournalIssue><Title>Movement disorders : official journal of the Movement Disorder Society</Title><ISOAbbreviation>Mov. Disord.</ISOAbbreviation></Journal><ArticleTitle>Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model.</ArticleTitle><Pagination><MedlinePgn>459-66</MedlinePgn></Pagination><Abstract><AbstractText>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. 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CompleteYN="Y"><Grant><GrantID>NS34886-01A2</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>UNITED STATES</Country><MedlineTA>Mov Disord</MedlineTA><NlmUniqueID>8610688</NlmUniqueID><ISSNLinking>0885-3185</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011954">Receptors, Dopamine</NameOfSubstance></Chemical><Chemical><RegistryNumber>46627O600J</RegistryNumber><NameOfSubstance 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UI="D009474">Neurons</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000187">drug effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000473">pathology</QualifierName><QualifierName MajorTopicYN="N" UI="Q000502">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D010302">Parkinson Disease, Secondary</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000139">chemically induced</QualifierName><QualifierName MajorTopicYN="N" UI="Q000473">pathology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000503">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D011954">Receptors, Dopamine</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000187">drug effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000502">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D012453">Saimiri</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D013378">Substantia Nigra</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000187">drug effects</QualifierName><QualifierName MajorTopicYN="N" UI="Q000473">pathology</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000503">physiopathology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2000</Year><Month>6</Month><Day>1</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2000</Year><Month>10</Month><Day>7</Day><Hour>11</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2000</Year><Month>6</Month><Day>1</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">10830409</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Janson, A M" sort="Janson, A M" uniqKey="Janson A" first="A M" last="Janson">A M Janson</name><name sortKey="Langston, W J" sort="Langston, W J" uniqKey="Langston W" first="W J" last="Langston">W J Langston</name><name sortKey="Mccormack, A" sort="Mccormack, A" uniqKey="Mccormack A" first="A" last="Mccormack">A. Mccormack</name><name sortKey="Petzinger, G" sort="Petzinger, G" uniqKey="Petzinger G" first="G" last="Petzinger">G. Petzinger</name><name sortKey="Quik, M" sort="Quik, M" uniqKey="Quik M" first="M" last="Quik">M. Quik</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Di Monte, D A" sort="Di Monte, D A" uniqKey="Di Monte D" first="D A" last="Di Monte">D A Di Monte</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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