Lentivector‐mediated delivery of GDNF protects complex motor functions relevant to human Parkinsonism in a rat lesion model
Identifieur interne : 000F88 ( Main/Corpus ); précédent : 000F87; suivant : 000F89Lentivector‐mediated delivery of GDNF protects complex motor functions relevant to human Parkinsonism in a rat lesion model
Auteurs : Eilís Dowd ; Christelle Monville ; Eduardo M. Torres ; Liang-Fong Wong ; Mimoun Azzouz ; Nicholas D. Mazarakis ; Stephen B. DunnettSource :
- European Journal of Neuroscience [ 0953-816X ] ; 2005-11.
English descriptors
Abstract
Although viral vector‐mediated delivery of glial cell‐line derived neurotrophic factor (GDNF) to the brain has considerable potential as a neuroprotective strategy in Parkinson's disease (PD), its ability to protect complex motor functions relevant to the human condition has yet to be established. In this study, we used an operant task that assesses the selection, initiation and execution of lateralized nose‐pokes in Lister Hooded rats to assess the efficacy with which complex behaviours are protected against neurotoxic lesions by prior injection of a lentiviral vector expressing GDNF. Unilateral injection of 6‐hydroxydopamine (6‐OHDA) into the medial forebrain bundle (MFB) caused rats to attempt fewer trials and to make more procedural errors. Lesioned rats also developed a pronounced ipsilateral bias, with a corresponding drop in contralateral accuracy. They were also slower to react to contralateral stimuli and to execute movements bilaterally. Rats that were pre‐treated 4 weeks prior to lesion surgery with an equine infectious anaemia virus (EIAV) vector carrying GDNF [EIAV‐GDNF, injected into the striatum and above the substantia nigra (SN)] performed significantly better on all of these parameters than control rats. In addition to the operant task, EIAV‐GDNF successfully rescued contralateral impairments in the corridor, staircase, stepping and cylinder tasks, and prevented drug‐induced rotational asymmetry. This study confirms that GDNF can protect against 6‐OHDA‐induced impairments in complex as well as simple behaviours, and reinforces the use of EIAV‐based vectors for the treatment of PD.
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DOI: 10.1111/j.1460-9568.2005.04414.x
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In this study, we used an operant task that assesses the selection, initiation and execution of lateralized nose‐pokes in Lister Hooded rats to assess the efficacy with which complex behaviours are protected against neurotoxic lesions by prior injection of a lentiviral vector expressing GDNF. Unilateral injection of 6‐hydroxydopamine (6‐OHDA) into the medial forebrain bundle (MFB) caused rats to attempt fewer trials and to make more procedural errors. Lesioned rats also developed a pronounced ipsilateral bias, with a corresponding drop in contralateral accuracy. They were also slower to react to contralateral stimuli and to execute movements bilaterally. Rats that were pre‐treated 4 weeks prior to lesion surgery with an equine infectious anaemia virus (EIAV) vector carrying GDNF [EIAV‐GDNF, injected into the striatum and above the substantia nigra (SN)] performed significantly better on all of these parameters than control rats. In addition to the operant task, EIAV‐GDNF successfully rescued contralateral impairments in the corridor, staircase, stepping and cylinder tasks, and prevented drug‐induced rotational asymmetry. This study confirms that GDNF can protect against 6‐OHDA‐induced impairments in complex as well as simple behaviours, and reinforces the use of EIAV‐based vectors for the treatment of PD.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Eilís Dowd</name><affiliations><json:string>Brain Repair Group, School of Biosciences, Cardiff University, Wales, UK</json:string></affiliations></json:item><json:item><name>Christelle Monville</name><affiliations><json:string>Brain Repair Group, School of Biosciences, Cardiff University, Wales, UK</json:string></affiliations></json:item><json:item><name>Eduardo M. 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In this study, we used an operant task that assesses the selection, initiation and execution of lateralized nose‐pokes in Lister Hooded rats to assess the efficacy with which complex behaviours are protected against neurotoxic lesions by prior injection of a lentiviral vector expressing GDNF. Unilateral injection of 6‐hydroxydopamine (6‐OHDA) into the medial forebrain bundle (MFB) caused rats to attempt fewer trials and to make more procedural errors. Lesioned rats also developed a pronounced ipsilateral bias, with a corresponding drop in contralateral accuracy. They were also slower to react to contralateral stimuli and to execute movements bilaterally. Rats that were pre‐treated 4 weeks prior to lesion surgery with an equine infectious anaemia virus (EIAV) vector carrying GDNF [EIAV‐GDNF, injected into the striatum and above the substantia nigra (SN)] performed significantly better on all of these parameters than control rats. In addition to the operant task, EIAV‐GDNF successfully rescued contralateral impairments in the corridor, staircase, stepping and cylinder tasks, and prevented drug‐induced rotational asymmetry. 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functions relevant to the human condition has yet to be established. In this study, we used an operant task that assesses the selection, initiation and execution of lateralized nose‐pokes in Lister Hooded rats to assess the efficacy with which complex behaviours are protected against neurotoxic lesions by prior injection of a lentiviral vector expressing GDNF. Unilateral injection of 6‐hydroxydopamine (6‐OHDA) into the medial forebrain bundle (MFB) caused rats to attempt fewer trials and to make more procedural errors. Lesioned rats also developed a pronounced ipsilateral bias, with a corresponding drop in contralateral accuracy. They were also slower to react to contralateral stimuli and to execute movements bilaterally. Rats that were pre‐treated 4 weeks prior to lesion surgery with an equine infectious anaemia virus (EIAV) vector carrying GDNF [EIAV‐GDNF, injected into the striatum and above the substantia nigra (SN)] performed significantly better on all of these parameters than control rats. In addition to the operant task, EIAV‐GDNF successfully rescued contralateral impairments in the corridor, staircase, stepping and cylinder tasks, and prevented drug‐induced rotational asymmetry. This study confirms that GDNF can protect against 6‐OHDA‐induced impairments in complex as well as simple behaviours, and reinforces the use of EIAV‐based vectors for the treatment of PD.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>6‐hydroxydopamine</term></item><item><term>lentivirus</term></item><item><term>medial forebrain bundle</term></item><item><term>Parkinson's disease</term></item><item><term>reaction time</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2005-11">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/636E57A40ABB7E7BC768B0650436667731A41D35/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="11010"><doi origin="wiley">10.1111/ejn.2005.22.issue-10</doi><numberingGroup><numbering type="journalVolume" number="22">22</numbering><numbering type="journalIssue" number="10">10</numbering></numberingGroup><coverDate startDate="2005-11">November 2005</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="20" status="forIssue"><doi origin="wiley">10.1111/j.1460-9568.2005.04414.x</doi><idGroup><id type="unit" value="EJN4414"></id></idGroup><countGroup><count type="pageTotal" number="9"></count></countGroup><titleGroup><title type="tocHeading1">Research Reports</title></titleGroup><eventGroup><event type="firstOnline" date="2005-11-23"></event><event type="publishedOnlineFinalForm" date="2005-11-23"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.2 mode:FullText source:FullText result:FullText" date="2010-03-02"></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="2587">2587</numbering><numbering type="pageLast" number="2595">2595</numbering></numberingGroup><correspondenceTo>Dr Eilís Dowd, as above.
E‐mail: <email>DowdE@cf.ac.uk</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:EJN.EJN4414.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received 29 April 2005, revised 22 August 2005, accepted 31 August 2005</unparsedEditorialHistory><countGroup><count type="figureTotal" number="8"></count><count type="tableTotal" number="0"></count><count type="formulaTotal" number="0"></count><count type="referenceTotal" number="43"></count><count type="wordTotal" number="5701"></count><count type="linksPubMed" number="0"></count><count type="linksCrossRef" number="0"></count></countGroup><titleGroup><title type="main">Lentivector‐mediated delivery of GDNF protects complex motor functions relevant to human Parkinsonism in a rat lesion model</title><title type="shortAuthors">E. Dowd <i>et al</i>.</title><title type="short">Functional neuroprotection by GDNF</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>Eilís</givenNames><familyName>Dowd</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>Christelle</givenNames><familyName>Monville</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1"><personName><givenNames>Eduardo M.</givenNames><familyName>Torres</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a2"><personName><givenNames>Liang‐Fong</givenNames><familyName>Wong</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a2"><personName><givenNames>Mimoun</givenNames><familyName>Azzouz</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a2"><personName><givenNames>Nicholas D.</givenNames><familyName>Mazarakis</familyName></personName></creator><creator creatorRole="author" xml:id="cr7" affiliationRef="#a1"><personName><givenNames>Stephen B.</givenNames><familyName>Dunnett</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="GB"><unparsedAffiliation>Brain Repair Group, School of Biosciences, Cardiff University, Wales, UK</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="GB"><unparsedAffiliation>Oxford BioMedica (UK) Ltd, The Oxford Science Park, Medawar Centre, Oxford, UK</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">6‐hydroxydopamine</keyword><keyword xml:id="k2">lentivirus</keyword><keyword xml:id="k3">medial forebrain bundle</keyword><keyword xml:id="k4">Parkinson's disease</keyword><keyword xml:id="k5">reaction time</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Although viral vector‐mediated delivery of glial cell‐line derived neurotrophic factor (GDNF) to the brain has considerable potential as a neuroprotective strategy in Parkinson's disease (PD), its ability to protect complex motor functions relevant to the human condition has yet to be established. In this study, we used an operant task that assesses the selection, initiation and execution of lateralized nose‐pokes in Lister Hooded rats to assess the efficacy with which complex behaviours are protected against neurotoxic lesions by prior injection of a lentiviral vector expressing GDNF. Unilateral injection of 6‐hydroxydopamine (6‐OHDA) into the medial forebrain bundle (MFB) caused rats to attempt fewer trials and to make more procedural errors. Lesioned rats also developed a pronounced ipsilateral bias, with a corresponding drop in contralateral accuracy. They were also slower to react to contralateral stimuli and to execute movements bilaterally. Rats that were pre‐treated 4 weeks prior to lesion surgery with an equine infectious anaemia virus (EIAV) vector carrying GDNF [EIAV‐GDNF, injected into the striatum and above the substantia nigra (SN)] performed significantly better on all of these parameters than control rats. In addition to the operant task, EIAV‐GDNF successfully rescued contralateral impairments in the corridor, staircase, stepping and cylinder tasks, and prevented drug‐induced rotational asymmetry. This study confirms that GDNF can protect against 6‐OHDA‐induced impairments in complex as well as simple behaviours, and reinforces the use of EIAV‐based vectors for the treatment of PD.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Lentivector‐mediated delivery of GDNF protects complex motor functions relevant to human Parkinsonism in a rat lesion model</title></titleInfo><titleInfo type="abbreviated"><title>Functional neuroprotection by GDNF</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Lentivector‐mediated delivery of GDNF protects complex motor functions relevant to human Parkinsonism in a rat lesion model</title></titleInfo><name type="personal"><namePart type="given">Eilís</namePart><namePart type="family">Dowd</namePart><affiliation>Brain Repair Group, School of Biosciences, Cardiff University, Wales, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christelle</namePart><namePart type="family">Monville</namePart><affiliation>Brain Repair Group, School of Biosciences, Cardiff University, Wales, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eduardo M.</namePart><namePart type="family">Torres</namePart><affiliation>Brain Repair Group, School of Biosciences, Cardiff University, Wales, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Liang‐Fong</namePart><namePart type="family">Wong</namePart><affiliation>Oxford BioMedica (UK) Ltd, The Oxford Science Park, Medawar Centre, Oxford, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mimoun</namePart><namePart type="family">Azzouz</namePart><affiliation>Oxford BioMedica (UK) Ltd, The Oxford Science Park, Medawar Centre, Oxford, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nicholas D.</namePart><namePart type="family">Mazarakis</namePart><affiliation>Oxford BioMedica (UK) Ltd, The Oxford Science Park, Medawar Centre, Oxford, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stephen B.</namePart><namePart type="family">Dunnett</namePart><affiliation>Brain Repair Group, School of Biosciences, Cardiff University, Wales, 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">2005-11</dateIssued><edition>Received 29 April 2005, revised 22 August 2005, accepted 31 August 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">8</extent><extent unit="references">43</extent><extent unit="words">5701</extent></physicalDescription><abstract lang="en">Although viral vector‐mediated delivery of glial cell‐line derived neurotrophic factor (GDNF) to the brain has considerable potential as a neuroprotective strategy in Parkinson's disease (PD), its ability to protect complex motor functions relevant to the human condition has yet to be established. In this study, we used an operant task that assesses the selection, initiation and execution of lateralized nose‐pokes in Lister Hooded rats to assess the efficacy with which complex behaviours are protected against neurotoxic lesions by prior injection of a lentiviral vector expressing GDNF. Unilateral injection of 6‐hydroxydopamine (6‐OHDA) into the medial forebrain bundle (MFB) caused rats to attempt fewer trials and to make more procedural errors. Lesioned rats also developed a pronounced ipsilateral bias, with a corresponding drop in contralateral accuracy. They were also slower to react to contralateral stimuli and to execute movements bilaterally. Rats that were pre‐treated 4 weeks prior to lesion surgery with an equine infectious anaemia virus (EIAV) vector carrying GDNF [EIAV‐GDNF, injected into the striatum and above the substantia nigra (SN)] performed significantly better on all of these parameters than control rats. In addition to the operant task, EIAV‐GDNF successfully rescued contralateral impairments in the corridor, staircase, stepping and cylinder tasks, and prevented drug‐induced rotational asymmetry. This study confirms that GDNF can protect against 6‐OHDA‐induced impairments in complex as well as simple behaviours, and reinforces the use of EIAV‐based vectors for the treatment of PD.</abstract><subject lang="en"><genre>Keywords</genre><topic>6‐hydroxydopamine</topic><topic>lentivirus</topic><topic>medial forebrain bundle</topic><topic>Parkinson's disease</topic><topic>reaction time</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>22</number></detail><detail type="issue"><caption>no.</caption><number>10</number></detail><extent unit="pages"><start>2587</start><end>2595</end><total>9</total></extent></part></relatedItem><identifier type="istex">636E57A40ABB7E7BC768B0650436667731A41D35</identifier><identifier type="DOI">10.1111/j.1460-9568.2005.04414.x</identifier><identifier type="ArticleID">EJN4414</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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