Riluzole reduces incidence of abnormal movements but not striatal cell death in a primate model of progressive striatal degeneration.
Identifieur interne : 001521 ( PubMed/Corpus ); précédent : 001520; suivant : 001522Riluzole reduces incidence of abnormal movements but not striatal cell death in a primate model of progressive striatal degeneration.
Auteurs : S. Palfi ; D. Riche ; E. Brouillet ; M C Guyot ; V. Mary ; F. Wahl ; M. Peschanski ; J M Stutzmann ; P. HantrayeSource :
- Experimental neurology [ 0014-4886 ] ; 1997.
English descriptors
- KwdEn :
- Acetylcholinesterase (analysis), Animals, Antiparkinson Agents (pharmacology), Apomorphine (pharmacology), Caudate Nucleus (drug effects), Caudate Nucleus (pathology), Corpus Striatum (drug effects), Corpus Striatum (pathology), Corpus Striatum (physiopathology), Movement Disorders (pathology), Movement Disorders (physiopathology), Movement Disorders (prevention & control), Nerve Degeneration (drug effects), Neurons (drug effects), Neurons (pathology), Neurons (physiology), Neuroprotective Agents (pharmacology), Neurotoxins, Nitro Compounds, Papio, Parkinson Disease, Secondary (pathology), Parkinson Disease, Secondary (physiopathology), Parkinson Disease, Secondary (prevention & control), Propionates, Putamen (drug effects), Putamen (pathology), Riluzole, Thiazoles (pharmacology).
- MESH :
- chemical , analysis : Acetylcholinesterase.
- chemical , pharmacology : Antiparkinson Agents, Apomorphine, Neuroprotective Agents, Thiazoles.
- drug effects : Caudate Nucleus, Corpus Striatum, Nerve Degeneration, Neurons, Putamen.
- pathology : Caudate Nucleus, Corpus Striatum, Movement Disorders, Neurons, Parkinson Disease, Secondary, Putamen.
- physiology : Neurons.
- physiopathology : Corpus Striatum, Movement Disorders, Parkinson Disease, Secondary.
- prevention & control : Movement Disorders, Parkinson Disease, Secondary.
- Animals, Neurotoxins, Nitro Compounds, Papio, Propionates, Riluzole.
Abstract
Riluzole has been shown recently to increase life expectancy in patients with amyotrophic lateral sclerosis. A number of experimental studies also suggest that this compound may be a neuroprotectant. We have investigated in baboons whether riluzole would protect striatal neurons from a prolonged 3-nitropropionic acid (3NP) treatment and ameliorate the associated motor symptoms. In animals receiving 3NP and the solvent of riluzole, 12 weeks of high-dose 3NP treatment resulted in the appearance of persistent leg dystonia and significant increases in the incidence of three categories of abnormal movements and in the dyskinesia index in the apomorphine test (0.5 mg/kg i.m.). Quantitative assessment of these behavioral deficits using a video movement analysis system demonstrated a significant decrease in locomotor activity and peak tangential velocity in 3NP-treated animals compared to controls. Histological analysis showed the presence of severe, bilateral, striatal lesions, localized in both caudate and putamen. Cotreatment with riluzole (4 mg/kg i.p., twice daily) significantly reduced the dyskinesia index (-35%, P < 0.02) in the apomorphine test. In the quantitative behavioral analysis, riluzole significantly ameliorated the decrease in peak tangential velocity (P < 0.02) but not the decrease in locomotor activity observed after 3NP. Comparative histological analysis of the two groups of treated animals did not demonstrate a clear neuroprotective effect of riluzole. The present study suggests that one potential therapeutic interest for riluzole in neurodegenerative disorders may reside in the reduction of motor symptoms associated with striatal lesions.
DOI: 10.1006/exnr.1997.6520
PubMed: 9225746
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pubmed:9225746Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Riluzole reduces incidence of abnormal movements but not striatal cell death in a primate model of progressive striatal degeneration.</title><author><name sortKey="Palfi, S" sort="Palfi, S" uniqKey="Palfi S" first="S" last="Palfi">S. Palfi</name><affiliation><nlm:affiliation>URA CEA/CNRS 2210 DRM, DSV, Service Hospitalier Frédéric Joliot, Orsay, France.</nlm:affiliation></affiliation></author><author><name sortKey="Riche, D" sort="Riche, D" uniqKey="Riche D" first="D" last="Riche">D. Riche</name></author><author><name sortKey="Brouillet, E" sort="Brouillet, E" uniqKey="Brouillet E" first="E" last="Brouillet">E. Brouillet</name></author><author><name sortKey="Guyot, M C" sort="Guyot, M C" uniqKey="Guyot M" first="M C" last="Guyot">M C Guyot</name></author><author><name sortKey="Mary, V" sort="Mary, V" uniqKey="Mary V" first="V" last="Mary">V. Mary</name></author><author><name sortKey="Wahl, F" sort="Wahl, F" uniqKey="Wahl F" first="F" last="Wahl">F. Wahl</name></author><author><name sortKey="Peschanski, M" sort="Peschanski, M" uniqKey="Peschanski M" first="M" last="Peschanski">M. Peschanski</name></author><author><name sortKey="Stutzmann, J M" sort="Stutzmann, J M" uniqKey="Stutzmann J" first="J M" last="Stutzmann">J M Stutzmann</name></author><author><name sortKey="Hantraye, P" sort="Hantraye, P" uniqKey="Hantraye P" first="P" last="Hantraye">P. Hantraye</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1997">1997</date><idno type="RBID">pubmed:9225746</idno><idno type="pmid">9225746</idno><idno type="doi">10.1006/exnr.1997.6520</idno><idno type="wicri:Area/PubMed/Corpus">001521</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001521</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Riluzole reduces incidence of abnormal movements but not striatal cell death in a primate model of progressive striatal degeneration.</title><author><name sortKey="Palfi, S" sort="Palfi, S" uniqKey="Palfi S" first="S" last="Palfi">S. Palfi</name><affiliation><nlm:affiliation>URA CEA/CNRS 2210 DRM, DSV, Service Hospitalier Frédéric Joliot, Orsay, France.</nlm:affiliation></affiliation></author><author><name sortKey="Riche, D" sort="Riche, D" uniqKey="Riche D" first="D" last="Riche">D. Riche</name></author><author><name sortKey="Brouillet, E" sort="Brouillet, E" uniqKey="Brouillet E" first="E" last="Brouillet">E. Brouillet</name></author><author><name sortKey="Guyot, M C" sort="Guyot, M C" uniqKey="Guyot M" first="M C" last="Guyot">M C Guyot</name></author><author><name sortKey="Mary, V" sort="Mary, V" uniqKey="Mary V" first="V" last="Mary">V. Mary</name></author><author><name sortKey="Wahl, F" sort="Wahl, F" uniqKey="Wahl F" first="F" last="Wahl">F. Wahl</name></author><author><name sortKey="Peschanski, M" sort="Peschanski, M" uniqKey="Peschanski M" first="M" last="Peschanski">M. Peschanski</name></author><author><name sortKey="Stutzmann, J M" sort="Stutzmann, J M" uniqKey="Stutzmann J" first="J M" last="Stutzmann">J M Stutzmann</name></author><author><name sortKey="Hantraye, P" sort="Hantraye, P" uniqKey="Hantraye P" first="P" last="Hantraye">P. Hantraye</name></author></analytic><series><title level="j">Experimental neurology</title><idno type="ISSN">0014-4886</idno><imprint><date when="1997" type="published">1997</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acetylcholinesterase (analysis)</term><term>Animals</term><term>Antiparkinson Agents (pharmacology)</term><term>Apomorphine (pharmacology)</term><term>Caudate Nucleus (drug effects)</term><term>Caudate Nucleus (pathology)</term><term>Corpus Striatum (drug effects)</term><term>Corpus Striatum (pathology)</term><term>Corpus Striatum (physiopathology)</term><term>Movement Disorders (pathology)</term><term>Movement Disorders (physiopathology)</term><term>Movement Disorders (prevention & control)</term><term>Nerve Degeneration (drug effects)</term><term>Neurons (drug effects)</term><term>Neurons (pathology)</term><term>Neurons (physiology)</term><term>Neuroprotective Agents (pharmacology)</term><term>Neurotoxins</term><term>Nitro Compounds</term><term>Papio</term><term>Parkinson Disease, Secondary (pathology)</term><term>Parkinson Disease, Secondary (physiopathology)</term><term>Parkinson Disease, Secondary (prevention & control)</term><term>Propionates</term><term>Putamen (drug effects)</term><term>Putamen (pathology)</term><term>Riluzole</term><term>Thiazoles (pharmacology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Acetylcholinesterase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiparkinson Agents</term><term>Apomorphine</term><term>Neuroprotective Agents</term><term>Thiazoles</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Caudate Nucleus</term><term>Corpus Striatum</term><term>Nerve Degeneration</term><term>Neurons</term><term>Putamen</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Caudate Nucleus</term><term>Corpus Striatum</term><term>Movement Disorders</term><term>Neurons</term><term>Parkinson Disease, Secondary</term><term>Putamen</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>Movement Disorders</term><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Movement Disorders</term><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Neurotoxins</term><term>Nitro Compounds</term><term>Papio</term><term>Propionates</term><term>Riluzole</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Riluzole has been shown recently to increase life expectancy in patients with amyotrophic lateral sclerosis. A number of experimental studies also suggest that this compound may be a neuroprotectant. We have investigated in baboons whether riluzole would protect striatal neurons from a prolonged 3-nitropropionic acid (3NP) treatment and ameliorate the associated motor symptoms. In animals receiving 3NP and the solvent of riluzole, 12 weeks of high-dose 3NP treatment resulted in the appearance of persistent leg dystonia and significant increases in the incidence of three categories of abnormal movements and in the dyskinesia index in the apomorphine test (0.5 mg/kg i.m.). Quantitative assessment of these behavioral deficits using a video movement analysis system demonstrated a significant decrease in locomotor activity and peak tangential velocity in 3NP-treated animals compared to controls. Histological analysis showed the presence of severe, bilateral, striatal lesions, localized in both caudate and putamen. Cotreatment with riluzole (4 mg/kg i.p., twice daily) significantly reduced the dyskinesia index (-35%, P < 0.02) in the apomorphine test. In the quantitative behavioral analysis, riluzole significantly ameliorated the decrease in peak tangential velocity (P < 0.02) but not the decrease in locomotor activity observed after 3NP. Comparative histological analysis of the two groups of treated animals did not demonstrate a clear neuroprotective effect of riluzole. The present study suggests that one potential therapeutic interest for riluzole in neurodegenerative disorders may reside in the reduction of motor symptoms associated with striatal lesions.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">9225746</PMID><DateCreated><Year>1997</Year><Month>08</Month><Day>07</Day></DateCreated><DateCompleted><Year>1997</Year><Month>08</Month><Day>07</Day></DateCompleted><DateRevised><Year>2015</Year><Month>11</Month><Day>19</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0014-4886</ISSN><JournalIssue CitedMedium="Print"><Volume>146</Volume><Issue>1</Issue><PubDate><Year>1997</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Experimental neurology</Title><ISOAbbreviation>Exp. Neurol.</ISOAbbreviation></Journal><ArticleTitle>Riluzole reduces incidence of abnormal movements but not striatal cell death in a primate model of progressive striatal degeneration.</ArticleTitle><Pagination><MedlinePgn>135-41</MedlinePgn></Pagination><Abstract><AbstractText>Riluzole has been shown recently to increase life expectancy in patients with amyotrophic lateral sclerosis. A number of experimental studies also suggest that this compound may be a neuroprotectant. We have investigated in baboons whether riluzole would protect striatal neurons from a prolonged 3-nitropropionic acid (3NP) treatment and ameliorate the associated motor symptoms. In animals receiving 3NP and the solvent of riluzole, 12 weeks of high-dose 3NP treatment resulted in the appearance of persistent leg dystonia and significant increases in the incidence of three categories of abnormal movements and in the dyskinesia index in the apomorphine test (0.5 mg/kg i.m.). Quantitative assessment of these behavioral deficits using a video movement analysis system demonstrated a significant decrease in locomotor activity and peak tangential velocity in 3NP-treated animals compared to controls. Histological analysis showed the presence of severe, bilateral, striatal lesions, localized in both caudate and putamen. Cotreatment with riluzole (4 mg/kg i.p., twice daily) significantly reduced the dyskinesia index (-35%, P < 0.02) in the apomorphine test. In the quantitative behavioral analysis, riluzole significantly ameliorated the decrease in peak tangential velocity (P < 0.02) but not the decrease in locomotor activity observed after 3NP. Comparative histological analysis of the two groups of treated animals did not demonstrate a clear neuroprotective effect of riluzole. The present study suggests that one potential therapeutic interest for riluzole in neurodegenerative disorders may reside in the reduction of motor symptoms associated with striatal lesions.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Palfi</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>URA CEA/CNRS 2210 DRM, DSV, Service Hospitalier Frédéric Joliot, Orsay, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Riche</LastName><ForeName>D</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Brouillet</LastName><ForeName>E</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Guyot</LastName><ForeName>M C</ForeName><Initials>MC</Initials></Author><Author ValidYN="Y"><LastName>Mary</LastName><ForeName>V</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Wahl</LastName><ForeName>F</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Peschanski</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Stutzmann</LastName><ForeName>J M</ForeName><Initials>JM</Initials></Author><Author ValidYN="Y"><LastName>Hantraye</LastName><ForeName>P</ForeName><Initials>P</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Exp Neurol</MedlineTA><NlmUniqueID>0370712</NlmUniqueID><ISSNLinking>0014-4886</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018696">Neuroprotective 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acid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000110" MajorTopicYN="N">Acetylcholinesterase</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000978" MajorTopicYN="N">Antiparkinson Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001058" MajorTopicYN="N">Apomorphine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002421" MajorTopicYN="N">Caudate Nucleus</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003342" MajorTopicYN="N">Corpus Striatum</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009069" MajorTopicYN="N">Movement Disorders</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009410" MajorTopicYN="N">Nerve Degeneration</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009474" MajorTopicYN="N">Neurons</DescriptorName><QualifierName 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MajorTopicYN="N">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011422" MajorTopicYN="N">Propionates</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011699" MajorTopicYN="N">Putamen</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019782" MajorTopicYN="N">Riluzole</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013844" MajorTopicYN="N">Thiazoles</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1997</Year><Month>7</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1997</Year><Month>7</Month><Day>1</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate 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