A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets
Identifieur interne : 002192 ( Main/Corpus ); précédent : 002191; suivant : 002193A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets
Auteurs : Mahmoud M. Iravani ; Emilie Syed ; Michael J. Jackson ; Louisa C. Johnston ; Lance A. Smith ; Peter JennerSource :
- European Journal of Neuroscience [ 0953-816X ] ; 2005-02.
English descriptors
Abstract
Standard MPTP treatment regimens in primates result in > 85% destruction of nigral dopaminergic neurons and the onset of marked motor deficits that respond to known symptomatic treatments for Parkinson's disease (PD). The extent of nigral degeneration reflects the late stages of PD rather than events occurring at its onset. We report on a modified MPTP treatment regimen that causes nigral dopaminergic degeneration in common marmosets equivalent to that occurring at the time of initiation of motor symptoms in man. Subcutaneous administration of MPTP 1 mg/kg for 3 consecutive days caused a reproducible 60% loss of nigral tyrosine hydroxylase (TH)‐positive cells, which occurred mainly in the calbindin‐D28k‐poor nigrosomes with a similar loss of TH‐immunoreactivity (TH‐ir) in the caudate nucleus and the putamen. The animals showed obvious motor abnormalities with reduced bursts of activity and the onset of motor disability. However, the loss of striatal terminals did not reflect early PD because a greater loss of TH‐ir occurred in the caudate nucleus than in the putamen and a marked reduction in TH‐ir occurred in striatal patches compared to the matrix. Examination of striatal fibres following a partial MPTP lesion showed a conspicuous increase in the number and the diameter of large branching fibres in the putaminal and to some extent caudatal matrix, pointing to a possible compensatory sprouting of dopaminergic terminals. In addition, these partially lesioned animals did not respond to acute treatment with L‐DOPA. This primate partial lesions model may be useful for examining potential neuroprotective or neurorestorative agents for PD.
Url:
DOI: 10.1111/j.1460-9568.2005.03915.x
Links to Exploration step
ISTEX:B8FE42FF7E932DE3757DE6A8A97DA2C96BC37BA4Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets</title><author><name sortKey="Iravani, Mahmoud M" sort="Iravani, Mahmoud M" uniqKey="Iravani M" first="Mahmoud M." last="Iravani">Mahmoud M. Iravani</name><affiliation><mods:affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</mods:affiliation></affiliation></author><author><name sortKey="Syed, Emilie" sort="Syed, Emilie" uniqKey="Syed E" first="Emilie" last="Syed">Emilie Syed</name><affiliation><mods:affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</mods:affiliation></affiliation></author><author><name sortKey="Jackson, Michael J" sort="Jackson, Michael J" uniqKey="Jackson M" first="Michael J." last="Jackson">Michael J. Jackson</name><affiliation><mods:affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</mods:affiliation></affiliation></author><author><name sortKey="Johnston, Louisa C" sort="Johnston, Louisa C" uniqKey="Johnston L" first="Louisa C." last="Johnston">Louisa C. Johnston</name><affiliation><mods:affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</mods:affiliation></affiliation></author><author><name sortKey="Smith, Lance A" sort="Smith, Lance A" uniqKey="Smith L" first="Lance A." last="Smith">Lance A. Smith</name><affiliation><mods:affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</mods:affiliation></affiliation></author><author><name sortKey="Jenner, Peter" sort="Jenner, Peter" uniqKey="Jenner P" first="Peter" last="Jenner">Peter Jenner</name><affiliation><mods:affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:B8FE42FF7E932DE3757DE6A8A97DA2C96BC37BA4</idno><date when="2005" year="2005">2005</date><idno type="doi">10.1111/j.1460-9568.2005.03915.x</idno><idno type="url">https://api.istex.fr/document/B8FE42FF7E932DE3757DE6A8A97DA2C96BC37BA4/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002192</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets</title><author><name sortKey="Iravani, Mahmoud M" sort="Iravani, Mahmoud M" uniqKey="Iravani M" first="Mahmoud M." last="Iravani">Mahmoud M. Iravani</name><affiliation><mods:affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</mods:affiliation></affiliation></author><author><name sortKey="Syed, Emilie" sort="Syed, Emilie" uniqKey="Syed E" first="Emilie" last="Syed">Emilie Syed</name><affiliation><mods:affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</mods:affiliation></affiliation></author><author><name sortKey="Jackson, Michael J" sort="Jackson, Michael J" uniqKey="Jackson M" first="Michael J." last="Jackson">Michael J. Jackson</name><affiliation><mods:affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</mods:affiliation></affiliation></author><author><name sortKey="Johnston, Louisa C" sort="Johnston, Louisa C" uniqKey="Johnston L" first="Louisa C." last="Johnston">Louisa C. Johnston</name><affiliation><mods:affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</mods:affiliation></affiliation></author><author><name sortKey="Smith, Lance A" sort="Smith, Lance A" uniqKey="Smith L" first="Lance A." last="Smith">Lance A. Smith</name><affiliation><mods:affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</mods:affiliation></affiliation></author><author><name sortKey="Jenner, Peter" sort="Jenner, Peter" uniqKey="Jenner P" first="Peter" last="Jenner">Peter Jenner</name><affiliation><mods:affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</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="2005-02">2005-02</date><biblScope unit="volume">21</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="841">841</biblScope><biblScope unit="page" to="854">854</biblScope></imprint><idno type="ISSN">0953-816X</idno></series><idno type="istex">B8FE42FF7E932DE3757DE6A8A97DA2C96BC37BA4</idno><idno type="DOI">10.1111/j.1460-9568.2005.03915.x</idno><idno type="ArticleID">EJN3915</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0953-816X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>MPTP</term><term>Parkinson's disease</term><term>common marmosets</term><term>partial lesion</term><term>striatum</term><term>substantia nigra</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Standard MPTP treatment regimens in primates result in > 85% destruction of nigral dopaminergic neurons and the onset of marked motor deficits that respond to known symptomatic treatments for Parkinson's disease (PD). The extent of nigral degeneration reflects the late stages of PD rather than events occurring at its onset. We report on a modified MPTP treatment regimen that causes nigral dopaminergic degeneration in common marmosets equivalent to that occurring at the time of initiation of motor symptoms in man. Subcutaneous administration of MPTP 1 mg/kg for 3 consecutive days caused a reproducible 60% loss of nigral tyrosine hydroxylase (TH)‐positive cells, which occurred mainly in the calbindin‐D28k‐poor nigrosomes with a similar loss of TH‐immunoreactivity (TH‐ir) in the caudate nucleus and the putamen. The animals showed obvious motor abnormalities with reduced bursts of activity and the onset of motor disability. However, the loss of striatal terminals did not reflect early PD because a greater loss of TH‐ir occurred in the caudate nucleus than in the putamen and a marked reduction in TH‐ir occurred in striatal patches compared to the matrix. Examination of striatal fibres following a partial MPTP lesion showed a conspicuous increase in the number and the diameter of large branching fibres in the putaminal and to some extent caudatal matrix, pointing to a possible compensatory sprouting of dopaminergic terminals. In addition, these partially lesioned animals did not respond to acute treatment with L‐DOPA. This primate partial lesions model may be useful for examining potential neuroprotective or neurorestorative agents for PD.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Mahmoud M. Iravani</name><affiliations><json:string>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</json:string></affiliations></json:item><json:item><name>Emilie Syed</name><affiliations><json:string>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</json:string></affiliations></json:item><json:item><name>Michael J. Jackson</name><affiliations><json:string>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</json:string></affiliations></json:item><json:item><name>Louisa C. Johnston</name><affiliations><json:string>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</json:string></affiliations></json:item><json:item><name>Lance A. Smith</name><affiliations><json:string>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</json:string></affiliations></json:item><json:item><name>Peter Jenner</name><affiliations><json:string>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>common marmosets</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MPTP</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>striatum</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>partial lesion</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item></subject><articleId><json:string>EJN3915</json:string></articleId><language><json:string>eng</json:string></language><abstract>Standard MPTP treatment regimens in primates result in > 85% destruction of nigral dopaminergic neurons and the onset of marked motor deficits that respond to known symptomatic treatments for Parkinson's disease (PD). The extent of nigral degeneration reflects the late stages of PD rather than events occurring at its onset. We report on a modified MPTP treatment regimen that causes nigral dopaminergic degeneration in common marmosets equivalent to that occurring at the time of initiation of motor symptoms in man. Subcutaneous administration of MPTP 1 mg/kg for 3 consecutive days caused a reproducible 60% loss of nigral tyrosine hydroxylase (TH)‐positive cells, which occurred mainly in the calbindin‐D28k‐poor nigrosomes with a similar loss of TH‐immunoreactivity (TH‐ir) in the caudate nucleus and the putamen. The animals showed obvious motor abnormalities with reduced bursts of activity and the onset of motor disability. However, the loss of striatal terminals did not reflect early PD because a greater loss of TH‐ir occurred in the caudate nucleus than in the putamen and a marked reduction in TH‐ir occurred in striatal patches compared to the matrix. Examination of striatal fibres following a partial MPTP lesion showed a conspicuous increase in the number and the diameter of large branching fibres in the putaminal and to some extent caudatal matrix, pointing to a possible compensatory sprouting of dopaminergic terminals. In addition, these partially lesioned animals did not respond to acute treatment with L‐DOPA. This primate partial lesions model may be useful for examining potential neuroprotective or neurorestorative agents for PD.</abstract><qualityIndicators><score>8.488</score><pdfVersion>1.4</pdfVersion><pdfPageSize>595 x 782 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>6</keywordCount><abstractCharCount>1661</abstractCharCount><pdfWordCount>5779</pdfWordCount><pdfCharCount>36198</pdfCharCount><pdfPageCount>14</pdfPageCount><abstractWordCount>249</abstractWordCount></qualityIndicators><title>A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets</title><genre><json:string>article</json:string></genre><host><volume>21</volume><publisherId><json:string>EJN</json:string></publisherId><pages><total>14</total><last>854</last><first>841</first></pages><issn><json:string>0953-816X</json:string></issn><issue>4</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><publicationDate>2005</publicationDate><copyrightDate>2005</copyrightDate><doi><json:string>10.1111/j.1460-9568.2005.03915.x</json:string></doi><id>B8FE42FF7E932DE3757DE6A8A97DA2C96BC37BA4</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/B8FE42FF7E932DE3757DE6A8A97DA2C96BC37BA4/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/B8FE42FF7E932DE3757DE6A8A97DA2C96BC37BA4/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/B8FE42FF7E932DE3757DE6A8A97DA2C96BC37BA4/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets</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">A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets</title><author><persName><forename type="first">Mahmoud M.</forename><surname>Iravani</surname></persName><affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</affiliation></author><author><persName><forename type="first">Emilie</forename><surname>Syed</surname></persName><affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</affiliation></author><author><persName><forename type="first">Michael J.</forename><surname>Jackson</surname></persName><affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</affiliation></author><author><persName><forename type="first">Louisa C.</forename><surname>Johnston</surname></persName><affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</affiliation></author><author><persName><forename type="first">Lance A.</forename><surname>Smith</surname></persName><affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</affiliation></author><author><persName><forename type="first">Peter</forename><surname>Jenner</surname></persName><affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</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="2005-02"></date><biblScope unit="volume">21</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="841">841</biblScope><biblScope unit="page" to="854">854</biblScope></imprint></monogr><idno type="istex">B8FE42FF7E932DE3757DE6A8A97DA2C96BC37BA4</idno><idno type="DOI">10.1111/j.1460-9568.2005.03915.x</idno><idno type="ArticleID">EJN3915</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2005</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Standard MPTP treatment regimens in primates result in > 85% destruction of nigral dopaminergic neurons and the onset of marked motor deficits that respond to known symptomatic treatments for Parkinson's disease (PD). The extent of nigral degeneration reflects the late stages of PD rather than events occurring at its onset. We report on a modified MPTP treatment regimen that causes nigral dopaminergic degeneration in common marmosets equivalent to that occurring at the time of initiation of motor symptoms in man. Subcutaneous administration of MPTP 1 mg/kg for 3 consecutive days caused a reproducible 60% loss of nigral tyrosine hydroxylase (TH)‐positive cells, which occurred mainly in the calbindin‐D28k‐poor nigrosomes with a similar loss of TH‐immunoreactivity (TH‐ir) in the caudate nucleus and the putamen. The animals showed obvious motor abnormalities with reduced bursts of activity and the onset of motor disability. However, the loss of striatal terminals did not reflect early PD because a greater loss of TH‐ir occurred in the caudate nucleus than in the putamen and a marked reduction in TH‐ir occurred in striatal patches compared to the matrix. Examination of striatal fibres following a partial MPTP lesion showed a conspicuous increase in the number and the diameter of large branching fibres in the putaminal and to some extent caudatal matrix, pointing to a possible compensatory sprouting of dopaminergic terminals. In addition, these partially lesioned animals did not respond to acute treatment with L‐DOPA. This primate partial lesions model may be useful for examining potential neuroprotective or neurorestorative agents for PD.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>common marmosets</term></item><item><term>MPTP</term></item><item><term>substantia nigra</term></item><item><term>striatum</term></item><item><term>partial lesion</term></item><item><term>Parkinson's disease</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2005-02">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/B8FE42FF7E932DE3757DE6A8A97DA2C96BC37BA4/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="02104"><doi origin="wiley">10.1111/ejn.2005.21.issue-4</doi><numberingGroup><numbering type="journalVolume" number="21">21</numbering><numbering type="journalIssue" number="4">4</numbering></numberingGroup><coverDate startDate="2005-02">February 2005</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="2" status="forIssue"><doi origin="wiley">10.1111/j.1460-9568.2005.03915.x</doi><idGroup><id type="unit" value="EJN3915"></id></idGroup><countGroup><count type="pageTotal" number="14"></count></countGroup><titleGroup><title type="tocHeading1">Research Reports</title></titleGroup><eventGroup><event type="firstOnline" date="2005-03-07"></event><event type="publishedOnlineFinalForm" date="2005-03-07"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.17 mode:FullText" date="2010-09-07"></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="841">841</numbering><numbering type="pageLast" number="854">854</numbering></numberingGroup><correspondenceTo>Professor Peter Jenner, as above.
E‐mail: <email>div.pharm@kcl.ac.uk</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:EJN.EJN3915.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received 1 July 2004, accepted 29 November 2004</unparsedEditorialHistory><countGroup><count type="figureTotal" number="9"></count><count type="tableTotal" number="0"></count><count type="formulaTotal" number="0"></count><count type="referenceTotal" number="45"></count><count type="wordTotal" number="4475"></count><count type="linksPubMed" number="0"></count><count type="linksCrossRef" number="0"></count></countGroup><titleGroup><title type="main">A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets</title><title type="shortAuthors">M. M. Iravani <i>et al.</i></title><title type="short">Partial nigral lesions in common marmosets</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#aff-1-1"><personName><givenNames>Mahmoud M.</givenNames><familyName>Iravani</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#aff-1-1"><personName><givenNames>Emilie</givenNames><familyName>Syed</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#aff-1-1"><personName><givenNames>Michael J.</givenNames><familyName>Jackson</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#aff-1-1"><personName><givenNames>Louisa C.</givenNames><familyName>Johnston</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#aff-1-1"><personName><givenNames>Lance A.</givenNames><familyName>Smith</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#aff-1-1"><personName><givenNames>Peter</givenNames><familyName>Jenner</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="aff-1-1" countryCode="GB"><unparsedAffiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">common marmosets</keyword><keyword xml:id="k2">MPTP</keyword><keyword xml:id="k3">substantia nigra</keyword><keyword xml:id="k4">striatum</keyword><keyword xml:id="k5">partial lesion</keyword><keyword xml:id="k6">Parkinson's disease</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Standard MPTP treatment regimens in primates result in > 85% destruction of nigral dopaminergic neurons and the onset of marked motor deficits that respond to known symptomatic treatments for Parkinson's disease (PD). The extent of nigral degeneration reflects the late stages of PD rather than events occurring at its onset. We report on a modified MPTP treatment regimen that causes nigral dopaminergic degeneration in common marmosets equivalent to that occurring at the time of initiation of motor symptoms in man. Subcutaneous administration of MPTP 1 mg/kg for 3 consecutive days caused a reproducible 60% loss of nigral tyrosine hydroxylase (TH)‐positive cells, which occurred mainly in the calbindin‐D<sub>28k</sub>‐poor nigrosomes with a similar loss of TH‐immunoreactivity (TH‐ir) in the caudate nucleus and the putamen. The animals showed obvious motor abnormalities with reduced bursts of activity and the onset of motor disability. However, the loss of striatal terminals did not reflect early PD because a greater loss of TH‐ir occurred in the caudate nucleus than in the putamen and a marked reduction in TH‐ir occurred in striatal patches compared to the matrix. Examination of striatal fibres following a partial MPTP lesion showed a conspicuous increase in the number and the diameter of large branching fibres in the putaminal and to some extent caudatal matrix, pointing to a possible compensatory sprouting of dopaminergic terminals. In addition, these partially lesioned animals did not respond to acute treatment with L‐DOPA. This primate partial lesions model may be useful for examining potential neuroprotective or neurorestorative agents for PD.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets</title></titleInfo><titleInfo type="abbreviated"><title>Partial nigral lesions in common marmosets</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets</title></titleInfo><name type="personal"><namePart type="given">Mahmoud M.</namePart><namePart type="family">Iravani</namePart><affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Emilie</namePart><namePart type="family">Syed</namePart><affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael J.</namePart><namePart type="family">Jackson</namePart><affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Louisa C.</namePart><namePart type="family">Johnston</namePart><affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lance A.</namePart><namePart type="family">Smith</namePart><affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter</namePart><namePart type="family">Jenner</namePart><affiliation>Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Science Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2005-02</dateIssued><edition>Received 1 July 2004, accepted 29 November 2004</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">9</extent><extent unit="references">45</extent><extent unit="words">4475</extent></physicalDescription><abstract lang="en">Standard MPTP treatment regimens in primates result in > 85% destruction of nigral dopaminergic neurons and the onset of marked motor deficits that respond to known symptomatic treatments for Parkinson's disease (PD). The extent of nigral degeneration reflects the late stages of PD rather than events occurring at its onset. We report on a modified MPTP treatment regimen that causes nigral dopaminergic degeneration in common marmosets equivalent to that occurring at the time of initiation of motor symptoms in man. Subcutaneous administration of MPTP 1 mg/kg for 3 consecutive days caused a reproducible 60% loss of nigral tyrosine hydroxylase (TH)‐positive cells, which occurred mainly in the calbindin‐D28k‐poor nigrosomes with a similar loss of TH‐immunoreactivity (TH‐ir) in the caudate nucleus and the putamen. The animals showed obvious motor abnormalities with reduced bursts of activity and the onset of motor disability. However, the loss of striatal terminals did not reflect early PD because a greater loss of TH‐ir occurred in the caudate nucleus than in the putamen and a marked reduction in TH‐ir occurred in striatal patches compared to the matrix. Examination of striatal fibres following a partial MPTP lesion showed a conspicuous increase in the number and the diameter of large branching fibres in the putaminal and to some extent caudatal matrix, pointing to a possible compensatory sprouting of dopaminergic terminals. In addition, these partially lesioned animals did not respond to acute treatment with L‐DOPA. This primate partial lesions model may be useful for examining potential neuroprotective or neurorestorative agents for PD.</abstract><subject lang="en"><genre>Keywords</genre><topic>common marmosets</topic><topic>MPTP</topic><topic>substantia nigra</topic><topic>striatum</topic><topic>partial lesion</topic><topic>Parkinson's disease</topic></subject><relatedItem type="host"><titleInfo><title>European Journal of Neuroscience</title></titleInfo><genre type="Journal">journal</genre><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>21</number></detail><detail type="issue"><caption>no.</caption><number>4</number></detail><extent unit="pages"><start>841</start><end>854</end><total>14</total></extent></part></relatedItem><identifier type="istex">B8FE42FF7E932DE3757DE6A8A97DA2C96BC37BA4</identifier><identifier type="DOI">10.1111/j.1460-9568.2005.03915.x</identifier><identifier type="ArticleID">EJN3915</identifier><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Science Ltd</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002192 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 002192 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:B8FE42FF7E932DE3757DE6A8A97DA2C96BC37BA4
|texte= A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets
}}
| This area was generated with Dilib version V0.6.23. |  |