Levodopa‐induced dyskinesia in MPTP‐treated macaques is not dependent on the extent and pattern of nigrostrial lesioning
Identifieur interne : 000D48 ( Istex/Corpus ); précédent : 000D47; suivant : 000D49Levodopa‐induced dyskinesia in MPTP‐treated macaques is not dependent on the extent and pattern of nigrostrial lesioning
Auteurs : Céline Guigoni ; Sandra Dovero ; Incarnation Aubert ; Qin Li ; Bernard H. Bioulac ; Bertrand Bloch ; Eugenia V. Gurevich ; Christian E. Gross ; Erwan BezardSource :
- European Journal of Neuroscience [ 0953-816X ] ; 2005-07.
English descriptors
Abstract
The extent of nigrostriatal denervation is presumed to play a role in the genesis of levodopa‐induced dyskinesia. Yet some parkinsonian patients who have been treated over a long period do not develop dyskinesia, raising the possibility that the pattern of denervation is as important as the extent of lesioning as a risk factor. Here we study the extent and pattern of nigrostriatal denervation in a homogeneous population of parkinsonian macaque monkeys chronically treated with levodopa. Based on the characteristics of the lesioning, non‐dyskinetic animals could not be differentiated from those with dyskinesia. Indeed, the number of tyrosine‐hydroxylase (TH)‐immunopositive neurons in the substantia nigra pars compacta, striatal dopamine transporter (DAT) binding and TH immunostaining, as well as the overall TH striatal content measured by Western blotting were identical. Moreover, the patterns of lesioning assessed by a detailed analysis of the TH‐ and DAT‐immunopositive striatal fibers were comparable in all functional quadrants and at all rostro‐caudal levels considered. These data indicate that neither the extent nor the pattern of nigrostriatal lesioning are sufficient to explain the occurrence of levodopa‐induced dyskinesia.
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DOI: 10.1111/j.1460-9568.2005.04196.x
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ISTEX:58BB6F6D34CE632A84E4B6186BEF91480ACEDCE4Le document en format XML
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Bioulac</name><affiliation><mods:affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</mods:affiliation></affiliation></author><author><name sortKey="Bloch, Bertrand" sort="Bloch, Bertrand" uniqKey="Bloch B" first="Bertrand" last="Bloch">Bertrand Bloch</name><affiliation><mods:affiliation>CNRS UMR 5541, Université Victor Segalen‐Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</mods:affiliation></affiliation></author><author><name sortKey="Gurevich, Eugenia V" sort="Gurevich, Eugenia V" uniqKey="Gurevich E" first="Eugenia V." last="Gurevich">Eugenia V. Gurevich</name><affiliation><mods:affiliation>Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA</mods:affiliation></affiliation></author><author><name sortKey="Gross, Christian E" sort="Gross, Christian E" uniqKey="Gross C" first="Christian E." last="Gross">Christian E. Gross</name><affiliation><mods:affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</mods:affiliation></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation><mods:affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">European Journal of Neuroscience</title><idno type="ISSN">0953-816X</idno><idno type="eISSN">1460-9568</idno><imprint><publisher>Blackwell Science Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2005-07">2005-07</date><biblScope unit="volume">22</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="283">283</biblScope><biblScope unit="page" to="287">287</biblScope></imprint><idno type="ISSN">0953-816X</idno></series><idno type="istex">58BB6F6D34CE632A84E4B6186BEF91480ACEDCE4</idno><idno type="DOI">10.1111/j.1460-9568.2005.04196.x</idno><idno type="ArticleID">EJN4196</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0953-816X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease</term><term>dopamine transporter</term><term>striatum</term><term>substantia nigra</term><term>tyrosine hydroxylase</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The extent of nigrostriatal denervation is presumed to play a role in the genesis of levodopa‐induced dyskinesia. Yet some parkinsonian patients who have been treated over a long period do not develop dyskinesia, raising the possibility that the pattern of denervation is as important as the extent of lesioning as a risk factor. Here we study the extent and pattern of nigrostriatal denervation in a homogeneous population of parkinsonian macaque monkeys chronically treated with levodopa. Based on the characteristics of the lesioning, non‐dyskinetic animals could not be differentiated from those with dyskinesia. Indeed, the number of tyrosine‐hydroxylase (TH)‐immunopositive neurons in the substantia nigra pars compacta, striatal dopamine transporter (DAT) binding and TH immunostaining, as well as the overall TH striatal content measured by Western blotting were identical. Moreover, the patterns of lesioning assessed by a detailed analysis of the TH‐ and DAT‐immunopositive striatal fibers were comparable in all functional quadrants and at all rostro‐caudal levels considered. These data indicate that neither the extent nor the pattern of nigrostriatal lesioning are sufficient to explain the occurrence of levodopa‐induced dyskinesia.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Céline Guigoni</name><affiliations><json:string>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</json:string></affiliations></json:item><json:item><name>Sandra Dovero</name><affiliations><json:string>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</json:string></affiliations></json:item><json:item><name>Incarnation Aubert</name><affiliations><json:string>CNRS UMR 5541, Université Victor Segalen‐Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</json:string></affiliations></json:item><json:item><name>Qin Li</name><affiliations><json:string>Laboratory Animal Research Centre, China Agricultural University, Beijing, China</json:string></affiliations></json:item><json:item><name>Bernard H. Bioulac</name><affiliations><json:string>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</json:string></affiliations></json:item><json:item><name>Bertrand Bloch</name><affiliations><json:string>CNRS UMR 5541, Université Victor Segalen‐Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</json:string></affiliations></json:item><json:item><name>Eugenia V. Gurevich</name><affiliations><json:string>Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA</json:string></affiliations></json:item><json:item><name>Christian E. Gross</name><affiliations><json:string>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</json:string></affiliations></json:item><json:item><name>Erwan Bezard</name><affiliations><json:string>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>dopamine transporter</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>striatum</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>substantia nigra</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>tyrosine hydroxylase</value></json:item></subject><articleId><json:string>EJN4196</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>shortCommunication</json:string></originalGenre><abstract>The extent of nigrostriatal denervation is presumed to play a role in the genesis of levodopa‐induced dyskinesia. Yet some parkinsonian patients who have been treated over a long period do not develop dyskinesia, raising the possibility that the pattern of denervation is as important as the extent of lesioning as a risk factor. Here we study the extent and pattern of nigrostriatal denervation in a homogeneous population of parkinsonian macaque monkeys chronically treated with levodopa. Based on the characteristics of the lesioning, non‐dyskinetic animals could not be differentiated from those with dyskinesia. Indeed, the number of tyrosine‐hydroxylase (TH)‐immunopositive neurons in the substantia nigra pars compacta, striatal dopamine transporter (DAT) binding and TH immunostaining, as well as the overall TH striatal content measured by Western blotting were identical. Moreover, the patterns of lesioning assessed by a detailed analysis of the TH‐ and DAT‐immunopositive striatal fibers were comparable in all functional quadrants and at all rostro‐caudal levels considered. These data indicate that neither the extent nor the pattern of nigrostriatal lesioning are sufficient to explain the occurrence of levodopa‐induced dyskinesia.</abstract><qualityIndicators><score>5.777</score><pdfVersion>1.4</pdfVersion><pdfPageSize>595 x 782 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1247</abstractCharCount><pdfWordCount>3141</pdfWordCount><pdfCharCount>20246</pdfCharCount><pdfPageCount>5</pdfPageCount><abstractWordCount>178</abstractWordCount></qualityIndicators><title>Levodopa‐induced dyskinesia in MPTP‐treated macaques is not dependent on the extent and pattern of nigrostrial lesioning</title><refBibs><json:item><author><json:item><name>I. Aubert</name></json:item><json:item><name>C. Guigoni</name></json:item><json:item><name>K. Hakansson</name></json:item><json:item><name>L. Qin</name></json:item><json:item><name>S. Dovero</name></json:item><json:item><name>N. Barthe</name></json:item><json:item><name>B.H. 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Neurobiol.</title></host><title>Wiring and Volume transmission in the central nervous system: the concept of closed and open synapses</title></json:item></refBibs><genre><json:string>brief-communication</json:string></genre><host><volume>22</volume><publisherId><json:string>EJN</json:string></publisherId><pages><total>5</total><last>287</last><first>283</first></pages><issn><json:string>0953-816X</json:string></issn><issue>1</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-9568</json:string></eissn><title>European Journal of Neuroscience</title><doi><json:string>10.1111/(ISSN)1460-9568</json:string></doi></host><categories><wos><json:string>science</json:string><json:string>neurosciences</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>neurology & neurosurgery</json:string></scienceMetrix></categories><publicationDate>2005</publicationDate><copyrightDate>2005</copyrightDate><doi><json:string>10.1111/j.1460-9568.2005.04196.x</json:string></doi><id>58BB6F6D34CE632A84E4B6186BEF91480ACEDCE4</id><score>0.14672902</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/58BB6F6D34CE632A84E4B6186BEF91480ACEDCE4/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/58BB6F6D34CE632A84E4B6186BEF91480ACEDCE4/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/58BB6F6D34CE632A84E4B6186BEF91480ACEDCE4/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Levodopa‐induced dyskinesia in MPTP‐treated macaques is not dependent on the extent and pattern of nigrostrial lesioning</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Science Ltd</publisher><pubPlace>Oxford, UK</pubPlace><availability><p>WILEY</p></availability><date>2005</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Levodopa‐induced dyskinesia in MPTP‐treated macaques is not dependent on the extent and pattern of nigrostrial lesioning</title><author xml:id="author-1"><persName><forename type="first">Céline</forename><surname>Guigoni</surname></persName><affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</affiliation></author><author xml:id="author-2"><persName><forename type="first">Sandra</forename><surname>Dovero</surname></persName><affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</affiliation></author><author xml:id="author-3"><persName><forename type="first">Incarnation</forename><surname>Aubert</surname></persName><affiliation>CNRS UMR 5541, Université Victor Segalen‐Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</affiliation></author><author xml:id="author-4"><persName><forename type="first">Qin</forename><surname>Li</surname></persName><affiliation>Laboratory Animal Research Centre, China Agricultural University, Beijing, China</affiliation></author><author xml:id="author-5"><persName><forename type="first">Bernard H.</forename><surname>Bioulac</surname></persName><affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</affiliation></author><author xml:id="author-6"><persName><forename type="first">Bertrand</forename><surname>Bloch</surname></persName><affiliation>CNRS UMR 5541, Université Victor Segalen‐Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</affiliation></author><author xml:id="author-7"><persName><forename type="first">Eugenia V.</forename><surname>Gurevich</surname></persName><affiliation>Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA</affiliation></author><author xml:id="author-8"><persName><forename type="first">Christian E.</forename><surname>Gross</surname></persName><affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</affiliation></author><author xml:id="author-9"><persName><forename type="first">Erwan</forename><surname>Bezard</surname></persName><affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</affiliation></author></analytic><monogr><title level="j">European Journal of Neuroscience</title><idno type="pISSN">0953-816X</idno><idno type="eISSN">1460-9568</idno><idno type="DOI">10.1111/(ISSN)1460-9568</idno><imprint><publisher>Blackwell Science Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2005-07"></date><biblScope unit="volume">22</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="283">283</biblScope><biblScope unit="page" to="287">287</biblScope></imprint></monogr><idno type="istex">58BB6F6D34CE632A84E4B6186BEF91480ACEDCE4</idno><idno type="DOI">10.1111/j.1460-9568.2005.04196.x</idno><idno type="ArticleID">EJN4196</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2005</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The extent of nigrostriatal denervation is presumed to play a role in the genesis of levodopa‐induced dyskinesia. Yet some parkinsonian patients who have been treated over a long period do not develop dyskinesia, raising the possibility that the pattern of denervation is as important as the extent of lesioning as a risk factor. Here we study the extent and pattern of nigrostriatal denervation in a homogeneous population of parkinsonian macaque monkeys chronically treated with levodopa. Based on the characteristics of the lesioning, non‐dyskinetic animals could not be differentiated from those with dyskinesia. Indeed, the number of tyrosine‐hydroxylase (TH)‐immunopositive neurons in the substantia nigra pars compacta, striatal dopamine transporter (DAT) binding and TH immunostaining, as well as the overall TH striatal content measured by Western blotting were identical. Moreover, the patterns of lesioning assessed by a detailed analysis of the TH‐ and DAT‐immunopositive striatal fibers were comparable in all functional quadrants and at all rostro‐caudal levels considered. These data indicate that neither the extent nor the pattern of nigrostriatal lesioning are sufficient to explain the occurrence of levodopa‐induced dyskinesia.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>dopamine transporter</term></item><item><term>Parkinson's disease</term></item><item><term>striatum</term></item><item><term>substantia nigra</term></item><item><term>tyrosine hydroxylase</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2005-07">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/58BB6F6D34CE632A84E4B6186BEF91480ACEDCE4/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Science Ltd</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1460-9568</doi><issn type="print">0953-816X</issn><issn type="electronic">1460-9568</issn><idGroup><id type="product" value="EJN"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="EUROPEAN JOURNAL OF NEUROSCIENCE">European Journal of Neuroscience</title></titleGroup></publicationMeta><publicationMeta level="part" position="07001"><doi origin="wiley">10.1111/ejn.2005.22.issue-1</doi><numberingGroup><numbering type="journalVolume" number="22">22</numbering><numbering type="journalIssue" number="1">1</numbering></numberingGroup><coverDate startDate="2005-07">July 2005</coverDate></publicationMeta><publicationMeta level="unit" type="shortCommunication" position="30" status="forIssue"><doi origin="wiley">10.1111/j.1460-9568.2005.04196.x</doi><idGroup><id type="unit" value="EJN4196"></id></idGroup><countGroup><count type="pageTotal" number="5"></count></countGroup><titleGroup><title type="tocHeading1">Short Communications</title></titleGroup><eventGroup><event type="firstOnline" date="2005-07-19"></event><event type="publishedOnlineFinalForm" date="2005-07-19"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.6 mode:FullText" date="2010-05-21"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:4.0.1" date="2014-03-12"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-16"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="283">283</numbering><numbering type="pageLast" number="287">287</numbering></numberingGroup><correspondenceTo>Dr E. Bezard, as above.
E‐mail: <email normalForm="erwan.bezard@umr5543.u-bordeaux2.fr">erwan.bezard@umr5543.u‐bordeaux2.fr</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:EJN.EJN4196.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received 9 March 2005, revised 13 April 2005, accepted 9 May 2005</unparsedEditorialHistory><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="0"></count><count type="formulaTotal" number="0"></count><count type="referenceTotal" number="29"></count><count type="wordTotal" number="2603"></count><count type="linksPubMed" number="0"></count><count type="linksCrossRef" number="0"></count></countGroup><titleGroup><title type="main">Levodopa‐induced dyskinesia in MPTP‐treated macaques is not dependent on the extent and pattern of nigrostrial lesioning</title><title type="shortAuthors">C. Guigoni <i>et al.</i></title><title type="short">Dyskinesia genesis and nigrostriatal lesion</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>Céline</givenNames><familyName>Guigoni</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>Sandra</givenNames><familyName>Dovero</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a2"><personName><givenNames>Incarnation</givenNames><familyName>Aubert</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a3"><personName><givenNames>Qin</givenNames><familyName>Li</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a1"><personName><givenNames>Bernard H.</givenNames><familyName>Bioulac</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a2"><personName><givenNames>Bertrand</givenNames><familyName>Bloch</familyName></personName></creator><creator creatorRole="author" xml:id="cr7" affiliationRef="#a4"><personName><givenNames>Eugenia V.</givenNames><familyName>Gurevich</familyName></personName></creator><creator creatorRole="author" xml:id="cr8" affiliationRef="#a1"><personName><givenNames>Christian E.</givenNames><familyName>Gross</familyName></personName></creator><creator creatorRole="author" xml:id="cr9" affiliationRef="#a1"><personName><givenNames>Erwan</givenNames><familyName>Bezard</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1"><unparsedAffiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="FR"><unparsedAffiliation>CNRS UMR 5541, Université Victor Segalen‐Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</unparsedAffiliation></affiliation><affiliation xml:id="a3" countryCode="CN"><unparsedAffiliation>Laboratory Animal Research Centre, China Agricultural University, Beijing, China</unparsedAffiliation></affiliation><affiliation xml:id="a4" countryCode="US"><unparsedAffiliation>Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">dopamine transporter</keyword><keyword xml:id="k2">Parkinson's disease</keyword><keyword xml:id="k3">striatum</keyword><keyword xml:id="k4">substantia nigra</keyword><keyword xml:id="k5">tyrosine hydroxylase</keyword></keywordGroup><supportingInformation><p><b>Fig. S1.</b> Pattern of lesion in control, MPTP‐lesioned untreated, MPTP‐lesioned LDOPA‐ treated non‐dyskinetic, and L‐DOPA‐treated dyskinetic monkeys. Representative high power photomicrographs of the striatal sections immunostained for TH shown in figure 1F (top row) and of adjacent striatal sections double‐immunolabelled (bottom) for TH (green) and DAT (red). Colocalisation of TH and DAT immunoreactivity produces a yellow signal. Scale bar = 55 ?m. Photomicrographs have been taken in all striatal quadrants at exactly the same position on each section to avoid selection bias: Cdl: caudate dorso‐lateral; Cdm: caudate dorso‐median; Cvl: caudate ventrolateral; Cvm: caudate ventro‐median; Pdl: putamen dorso‐lateral; Pdm: putamen dorso‐median; Pvl: putamen ventro‐lateral; Pvm: putamen ventro‐median.</p><supportingInfoItem><mediaResource alt="supporting info item" href="urn-x:wiley:0953816X:media:ejn4196:EJN_4196_sm_FigS1"></mediaResource><caption>Supporting info item</caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>The extent of nigrostriatal denervation is presumed to play a role in the genesis of levodopa‐induced dyskinesia. Yet some parkinsonian patients who have been treated over a long period do not develop dyskinesia, raising the possibility that the pattern of denervation is as important as the extent of lesioning as a risk factor. Here we study the extent and pattern of nigrostriatal denervation in a homogeneous population of parkinsonian macaque monkeys chronically treated with levodopa. Based on the characteristics of the lesioning, non‐dyskinetic animals could not be differentiated from those with dyskinesia. Indeed, the number of tyrosine‐hydroxylase (TH)‐immunopositive neurons in the substantia nigra pars compacta, striatal dopamine transporter (DAT) binding and TH immunostaining, as well as the overall TH striatal content measured by Western blotting were identical. Moreover, the patterns of lesioning assessed by a detailed analysis of the TH‐ and DAT‐immunopositive striatal fibers were comparable in all functional quadrants and at all rostro‐caudal levels considered. These data indicate that neither the extent nor the pattern of nigrostriatal lesioning are sufficient to explain the occurrence of levodopa‐induced dyskinesia.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Levodopa‐induced dyskinesia in MPTP‐treated macaques is not dependent on the extent and pattern of nigrostrial lesioning</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Dyskinesia genesis and nigrostriatal lesion</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Levodopa‐induced dyskinesia in MPTP‐treated macaques is not dependent on the extent and pattern of nigrostrial lesioning</title></titleInfo><name type="personal"><namePart type="given">Céline</namePart><namePart type="family">Guigoni</namePart><affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sandra</namePart><namePart type="family">Dovero</namePart><affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Incarnation</namePart><namePart type="family">Aubert</namePart><affiliation>CNRS UMR 5541, Université Victor Segalen‐Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Qin</namePart><namePart type="family">Li</namePart><affiliation>Laboratory Animal Research Centre, China Agricultural University, Beijing, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bernard H.</namePart><namePart type="family">Bioulac</namePart><affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bertrand</namePart><namePart type="family">Bloch</namePart><affiliation>CNRS UMR 5541, Université Victor Segalen‐Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eugenia V.</namePart><namePart type="family">Gurevich</namePart><affiliation>Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christian E.</namePart><namePart type="family">Gross</namePart><affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Erwan</namePart><namePart type="family">Bezard</namePart><affiliation>Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="brief-communication" displayLabel="shortCommunication"></genre><originInfo><publisher>Blackwell Science Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2005-07</dateIssued><edition>Received 9 March 2005, revised 13 April 2005, accepted 9 May 2005</edition><copyrightDate encoding="w3cdtf">2005</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">3</extent><extent unit="references">29</extent><extent unit="words">2603</extent></physicalDescription><abstract lang="en">The extent of nigrostriatal denervation is presumed to play a role in the genesis of levodopa‐induced dyskinesia. Yet some parkinsonian patients who have been treated over a long period do not develop dyskinesia, raising the possibility that the pattern of denervation is as important as the extent of lesioning as a risk factor. Here we study the extent and pattern of nigrostriatal denervation in a homogeneous population of parkinsonian macaque monkeys chronically treated with levodopa. Based on the characteristics of the lesioning, non‐dyskinetic animals could not be differentiated from those with dyskinesia. Indeed, the number of tyrosine‐hydroxylase (TH)‐immunopositive neurons in the substantia nigra pars compacta, striatal dopamine transporter (DAT) binding and TH immunostaining, as well as the overall TH striatal content measured by Western blotting were identical. Moreover, the patterns of lesioning assessed by a detailed analysis of the TH‐ and DAT‐immunopositive striatal fibers were comparable in all functional quadrants and at all rostro‐caudal levels considered. These data indicate that neither the extent nor the pattern of nigrostriatal lesioning are sufficient to explain the occurrence of levodopa‐induced dyskinesia.</abstract><subject lang="en"><genre>keywords</genre><topic>dopamine transporter</topic><topic>Parkinson's disease</topic><topic>striatum</topic><topic>substantia nigra</topic><topic>tyrosine hydroxylase</topic></subject><relatedItem type="host"><titleInfo><title>European Journal of Neuroscience</title></titleInfo><genre type="journal">journal</genre><note type="content"> Fig. S1. Pattern of lesion in control, MPTP‐lesioned untreated, MPTP‐lesioned LDOPA‐ treated non‐dyskinetic, and L‐DOPA‐treated dyskinetic monkeys. Representative high power photomicrographs of the striatal sections immunostained for TH shown in figure 1F (top row) and of adjacent striatal sections double‐immunolabelled (bottom) for TH (green) and DAT (red). Colocalisation of TH and DAT immunoreactivity produces a yellow signal. Scale bar = 55 ?m. Photomicrographs have been taken in all striatal quadrants at exactly the same position on each section to avoid selection bias: Cdl: caudate dorso‐lateral; Cdm: caudate dorso‐median; Cvl: caudate ventrolateral; Cvm: caudate ventro‐median; Pdl: putamen dorso‐lateral; Pdm: putamen dorso‐median; Pvl: putamen ventro‐lateral; Pvm: putamen ventro‐median.Supporting Info Item: Supporting info item - </note><identifier type="ISSN">0953-816X</identifier><identifier type="eISSN">1460-9568</identifier><identifier type="DOI">10.1111/(ISSN)1460-9568</identifier><identifier type="PublisherID">EJN</identifier><part><date>2005</date><detail type="volume"><caption>vol.</caption><number>22</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>283</start><end>287</end><total>5</total></extent></part></relatedItem><identifier type="istex">58BB6F6D34CE632A84E4B6186BEF91480ACEDCE4</identifier><identifier type="DOI">10.1111/j.1460-9568.2005.04196.x</identifier><identifier type="ArticleID">EJN4196</identifier><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Science Ltd</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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