Metabotropic glutamate receptor type 5 in levodopa-induced motor complications
Identifieur interne : 001937 ( Main/Exploration ); précédent : 001936; suivant : 001938Metabotropic glutamate receptor type 5 in levodopa-induced motor complications
Auteurs : Bazoumana Ouattara [Canada] ; Laurent Gregoire [Canada] ; Marc Morissette [Canada] ; Fabrizio Gasparini [Suisse] ; Ivo Vranesic [Suisse] ; Graeme Bilbe [Suisse] ; Donald R. Johns [Suisse] ; Alex Rajput [Canada] ; Oleh. Hornykiewicz [Autriche] ; Ali H. Rajput [Canada] ; Baltazar Gomez-Mancilla [Suisse] ; Therese Di Paolo [Canada]Source :
- Neurobiology of aging [ 0197-4580 ] ; 2011.
Descripteurs français
- Pascal (Inist)
- Wicri :
English descriptors
- KwdEn :
Abstract
Metabotropic glutamate receptors type 5 (mGluR5) are implicated in regulation of synaptic plasticity and learning, and were the focus of our investigation in human Parkinson's disease (PD) patients with dyskinesias and wearing-off, and in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) monkeys with dyskinesias. Using the selective mGluR5 ligand [3H]ABP688 autoradiography, we measured mGluR5 in brain slices from 11 normal and 14 PD patients and from MPTP monkeys, in relation to motor complications (dyskinesias and wearing-off) associated with treatment with L-dopa. In 16 monkeys with a bilateral MPTP lesion and four controls, [3H]ABP688 specific binding was elevated in the striatum of dyskinetic L-dopa-treated MPTP monkeys but not in MPTP monkeys without dyskinesias compared to controls. PD patients with motor complications (either dyskinesias or wearing-off) had higher [3H]ABP688 specific binding compared to those without motor complications and controls in putamen, external and internal globus pallidus. Elevated glutamatergic transmission as measured with increased mGluR5 specific binding was associated with motor complications and its antagonism could be targeted for their treatment.
Affiliations:
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Hornykiewicz</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Institute for Brain Research, Faculty of Medicine, University of Vienna</s1><s2>Vienna</s2><s3>AUT</s3><sZ>9 aut.</sZ></inist:fA14><country>Autriche</country><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. 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when="2011">2011</date><idno type="stanalyst">PASCAL 11-0338872 INIST</idno><idno type="RBID">Pascal:11-0338872</idno><idno type="wicri:Area/PascalFrancis/Corpus">000302</idno><idno type="wicri:Area/PascalFrancis/Curation">000961</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000256</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000256</idno><idno type="wicri:doubleKey">0197-4580:2011:Ouattara B:metabotropic:glutamate:receptor</idno><idno type="wicri:Area/Main/Merge">001A31</idno><idno type="wicri:Area/Main/Curation">001937</idno><idno type="wicri:Area/Main/Exploration">001937</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Metabotropic glutamate receptor type 5 in levodopa-induced motor complications</title><author><name sortKey="Ouattara, Bazoumana" sort="Ouattara, Bazoumana" uniqKey="Ouattara B" first="Bazoumana" last="Ouattara">Bazoumana Ouattara</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Genomic Research Center, Laval University Medical Center (CHUL</s1><s2>Quebec (QC)</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec (QC)</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Quebec (QC</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec (QC</wicri:noRegion></affiliation></author><author><name sortKey="Gregoire, Laurent" sort="Gregoire, Laurent" uniqKey="Gregoire L" first="Laurent" last="Gregoire">Laurent Gregoire</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Genomic Research Center, Laval University Medical Center (CHUL</s1><s2>Quebec (QC)</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec (QC)</wicri:noRegion></affiliation></author><author><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Genomic Research Center, Laval University Medical Center (CHUL</s1><s2>Quebec (QC)</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec (QC)</wicri:noRegion></affiliation></author><author><name sortKey="Gasparini, Fabrizio" sort="Gasparini, Fabrizio" uniqKey="Gasparini F" first="Fabrizio" last="Gasparini">Fabrizio Gasparini</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Research, Novartis Institutes for BioMedical Research</s1><s2>4002 Basel</s2><s3>CHE</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Suisse</country><wicri:noRegion>4002 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Vranesic, Ivo" sort="Vranesic, Ivo" uniqKey="Vranesic I" first="Ivo" last="Vranesic">Ivo Vranesic</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Research, Novartis Institutes for BioMedical Research</s1><s2>4002 Basel</s2><s3>CHE</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Suisse</country><wicri:noRegion>4002 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Bilbe, Graeme" sort="Bilbe, Graeme" uniqKey="Bilbe G" first="Graeme" last="Bilbe">Graeme Bilbe</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Research, Novartis Institutes for BioMedical Research</s1><s2>4002 Basel</s2><s3>CHE</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Suisse</country><wicri:noRegion>4002 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Johns, Donald R" sort="Johns, Donald R" uniqKey="Johns D" first="Donald R." last="Johns">Donald R. Johns</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Research, Novartis Institutes for BioMedical Research</s1><s2>4002 Basel</s2><s3>CHE</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Suisse</country><wicri:noRegion>4002 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Rajput, Alex" sort="Rajput, Alex" uniqKey="Rajput A" first="Alex" last="Rajput">Alex Rajput</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Division of Neurology, University of Saskatchewan, Royal University Hospital</s1><s2>Saskatoon</s2><s3>CAN</s3><sZ>8 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Hornykiewicz, Oleh" sort="Hornykiewicz, Oleh" uniqKey="Hornykiewicz O" first="Oleh." last="Hornykiewicz">Oleh. Hornykiewicz</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Institute for Brain Research, Faculty of Medicine, University of Vienna</s1><s2>Vienna</s2><s3>AUT</s3><sZ>9 aut.</sZ></inist:fA14><country>Autriche</country><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. Rajput</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Division of Neurology, University of Saskatchewan, Royal University Hospital</s1><s2>Saskatoon</s2><s3>CAN</s3><sZ>8 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Gomez Mancilla, Baltazar" sort="Gomez Mancilla, Baltazar" uniqKey="Gomez Mancilla B" first="Baltazar" last="Gomez-Mancilla">Baltazar Gomez-Mancilla</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Neuroscience Research, Novartis Institutes for BioMedical Research</s1><s2>4002 Basel</s2><s3>CHE</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Suisse</country><wicri:noRegion>4002 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Therese" last="Di Paolo">Therese Di Paolo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Genomic Research Center, Laval University Medical Center (CHUL</s1><s2>Quebec (QC)</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec (QC)</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Faculty of Pharmacy, Laval University</s1><s2>Quebec (QC</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec (QC</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Division of Neurology, University of Saskatchewan, Royal University Hospital</s1><s2>Saskatoon</s2><s3>CAN</s3><sZ>8 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Neurobiology of aging</title><title level="j" type="abbreviated">Neurobiol. aging</title><idno type="ISSN">0197-4580</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Neurobiology of aging</title><title level="j" type="abbreviated">Neurobiol. aging</title><idno type="ISSN">0197-4580</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Glutamate receptor</term><term>Human</term><term>Levodopa</term><term>Metabotropic receptor</term><term>Monkey</term><term>Neurotoxin</term><term>Senescence</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Récepteur métabotropique</term><term>Récepteur glutamate</term><term>Lévodopa</term><term>Neurotoxine</term><term>Sénescence</term><term>Homme</term><term>Singe</term><term>MPTP</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term><term>Singe</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Metabotropic glutamate receptors type 5 (mGluR5) are implicated in regulation of synaptic plasticity and learning, and were the focus of our investigation in human Parkinson's disease (PD) patients with dyskinesias and wearing-off, and in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) monkeys with dyskinesias. Using the selective mGluR5 ligand [<sup>3</sup>H]ABP688 autoradiography, we measured mGluR5 in brain slices from 11 normal and 14 PD patients and from MPTP monkeys, in relation to motor complications (dyskinesias and wearing-off) associated with treatment with <sub>L</sub>-dopa. In 16 monkeys with a bilateral MPTP lesion and four controls, [<sup>3</sup>H]ABP688 specific binding was elevated in the striatum of dyskinetic <sub>L</sub>-dopa-treated MPTP monkeys but not in MPTP monkeys without dyskinesias compared to controls. PD patients with motor complications (either dyskinesias or wearing-off) had higher [<sup>3</sup>H]ABP688 specific binding compared to those without motor complications and controls in putamen, external and internal globus pallidus. Elevated glutamatergic transmission as measured with increased mGluR5 specific binding was associated with motor complications and its antagonism could be targeted for their treatment.</div></front></TEI><affiliations><list><country><li>Autriche</li><li>Canada</li><li>Suisse</li></country><region><li>Vienne (Autriche)</li></region><settlement><li>Vienne (Autriche)</li></settlement></list><tree><country name="Canada"><noRegion><name sortKey="Ouattara, Bazoumana" sort="Ouattara, Bazoumana" uniqKey="Ouattara B" first="Bazoumana" last="Ouattara">Bazoumana Ouattara</name></noRegion><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Therese" last="Di Paolo">Therese Di Paolo</name><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Therese" last="Di Paolo">Therese Di Paolo</name><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Therese" last="Di Paolo">Therese Di Paolo</name><name sortKey="Gregoire, Laurent" sort="Gregoire, Laurent" uniqKey="Gregoire L" first="Laurent" last="Gregoire">Laurent Gregoire</name><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name><name sortKey="Ouattara, Bazoumana" sort="Ouattara, Bazoumana" uniqKey="Ouattara B" first="Bazoumana" last="Ouattara">Bazoumana Ouattara</name><name sortKey="Rajput, Alex" sort="Rajput, Alex" uniqKey="Rajput A" first="Alex" last="Rajput">Alex Rajput</name><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. Rajput</name></country><country name="Suisse"><noRegion><name sortKey="Gasparini, Fabrizio" sort="Gasparini, Fabrizio" uniqKey="Gasparini F" first="Fabrizio" last="Gasparini">Fabrizio Gasparini</name></noRegion><name sortKey="Bilbe, Graeme" sort="Bilbe, Graeme" uniqKey="Bilbe G" first="Graeme" last="Bilbe">Graeme Bilbe</name><name sortKey="Gomez Mancilla, Baltazar" sort="Gomez Mancilla, Baltazar" uniqKey="Gomez Mancilla B" first="Baltazar" last="Gomez-Mancilla">Baltazar Gomez-Mancilla</name><name sortKey="Johns, Donald R" sort="Johns, Donald R" uniqKey="Johns D" first="Donald R." last="Johns">Donald R. Johns</name><name sortKey="Vranesic, Ivo" sort="Vranesic, Ivo" uniqKey="Vranesic I" first="Ivo" last="Vranesic">Ivo Vranesic</name></country><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Hornykiewicz, Oleh" sort="Hornykiewicz, Oleh" uniqKey="Hornykiewicz O" first="Oleh." last="Hornykiewicz">Oleh. 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