Dopaminergic and non‐dopaminergic pharmacological hypotheses for gait disorders in Parkinson’s disease
Identifieur interne : 000582 ( Main/Corpus ); précédent : 000581; suivant : 000583Dopaminergic and non‐dopaminergic pharmacological hypotheses for gait disorders in Parkinson’s disease
Auteurs : David Devos ; L. Defebvre ; R. BordetSource :
- Fundamental & Clinical Pharmacology [ 0767-3981 ] ; 2010-08.
English descriptors
Abstract
Gait disorders form one component of the axial disorders observed in Parkinson’s disease (PD). Indeed, short steps with a forward‐leaning stance are diagnostic criteria for PD in the early stages of the condition. Gait disorders also represent a major source of therapeutic failure in the advanced stages of PD (with the appearance of freezing of gait and falls) because they do not respond optimally to the two hand late‐stage therapeutics – levodopa and electrical subthalamic nucleus (STN) stimulation. The late onset of doparesistance in these disorders may be linked to propagation of neurodegeneration to structures directly involved in gait control and to non‐dopaminergic neurotransmitter systems. The coeruleus locus (a source of noradrenaline) is rapidly and severely affected, leading to a major motor impact. The pedunculopontine nucleus (PPN) and lateral pontine tegmentum (rich in acetylcholine) are both involved in gait. Degenerative damage to the serotoninergic raphe nuclei appears to be less severe, although serotonin‐dopamine interactions are numerous and complex. Lastly, dopaminergic depletion leads to glutamatergic hyperactivity of the efferent pathways from the the STN to the PPN. However, the relationships between the various parkinsonian symptoms (and particularly gait disorders) and these pharmacological targets have yet to be fully elucidated. The goal of this review is to develop the various pathophysiological hypotheses published to date, in order to underpin and justify ongoing fundamental research and clinical trials in this disease area.
Url:
DOI: 10.1111/j.1472-8206.2009.00798.x
Links to Exploration step
ISTEX:E30C8267F686573C916FD9B8D19D566FFA36D320Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Dopaminergic and non‐dopaminergic pharmacological hypotheses for gait disorders in Parkinson’s disease</title><author><name sortKey="Devos, David" sort="Devos, David" uniqKey="Devos D" first="David" last="Devos">David Devos</name><affiliation><mods:affiliation>Department of Neurology and Movement Disorders, EA2683, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Defebvre, L" sort="Defebvre, L" uniqKey="Defebvre L" first="L." last="Defebvre">L. Defebvre</name><affiliation><mods:affiliation>Department of Neurology and Movement Disorders, EA2683, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Bordet, R" sort="Bordet, R" uniqKey="Bordet R" first="R." last="Bordet">R. Bordet</name><affiliation><mods:affiliation>Department of Pharmacology Medical, EA 1046, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:E30C8267F686573C916FD9B8D19D566FFA36D320</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1111/j.1472-8206.2009.00798.x</idno><idno type="url">https://api.istex.fr/document/E30C8267F686573C916FD9B8D19D566FFA36D320/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000582</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Dopaminergic and non‐dopaminergic pharmacological hypotheses for gait disorders in Parkinson’s disease</title><author><name sortKey="Devos, David" sort="Devos, David" uniqKey="Devos D" first="David" last="Devos">David Devos</name><affiliation><mods:affiliation>Department of Neurology and Movement Disorders, EA2683, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Defebvre, L" sort="Defebvre, L" uniqKey="Defebvre L" first="L." last="Defebvre">L. Defebvre</name><affiliation><mods:affiliation>Department of Neurology and Movement Disorders, EA2683, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Bordet, R" sort="Bordet, R" uniqKey="Bordet R" first="R." last="Bordet">R. Bordet</name><affiliation><mods:affiliation>Department of Pharmacology Medical, EA 1046, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Fundamental & Clinical Pharmacology</title><idno type="ISSN">0767-3981</idno><idno type="eISSN">1472-8206</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2010-08">2010-08</date><biblScope unit="volume">24</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="407">407</biblScope><biblScope unit="page" to="421">421</biblScope></imprint><idno type="ISSN">0767-3981</idno></series><idno type="istex">E30C8267F686573C916FD9B8D19D566FFA36D320</idno><idno type="DOI">10.1111/j.1472-8206.2009.00798.x</idno><idno type="ArticleID">FCP798</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0767-3981</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson’s disease</term><term>dopamine</term><term>gait disorders</term><term>glutamate</term><term>noradrenaline</term><term>pharmacology</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Gait disorders form one component of the axial disorders observed in Parkinson’s disease (PD). Indeed, short steps with a forward‐leaning stance are diagnostic criteria for PD in the early stages of the condition. Gait disorders also represent a major source of therapeutic failure in the advanced stages of PD (with the appearance of freezing of gait and falls) because they do not respond optimally to the two hand late‐stage therapeutics – levodopa and electrical subthalamic nucleus (STN) stimulation. The late onset of doparesistance in these disorders may be linked to propagation of neurodegeneration to structures directly involved in gait control and to non‐dopaminergic neurotransmitter systems. The coeruleus locus (a source of noradrenaline) is rapidly and severely affected, leading to a major motor impact. The pedunculopontine nucleus (PPN) and lateral pontine tegmentum (rich in acetylcholine) are both involved in gait. Degenerative damage to the serotoninergic raphe nuclei appears to be less severe, although serotonin‐dopamine interactions are numerous and complex. Lastly, dopaminergic depletion leads to glutamatergic hyperactivity of the efferent pathways from the the STN to the PPN. However, the relationships between the various parkinsonian symptoms (and particularly gait disorders) and these pharmacological targets have yet to be fully elucidated. The goal of this review is to develop the various pathophysiological hypotheses published to date, in order to underpin and justify ongoing fundamental research and clinical trials in this disease area.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>David Devos</name><affiliations><json:string>Department of Neurology and Movement Disorders, EA2683, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</json:string></affiliations></json:item><json:item><name>L. Defebvre</name><affiliations><json:string>Department of Neurology and Movement Disorders, EA2683, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</json:string></affiliations></json:item><json:item><name>R. Bordet</name><affiliations><json:string>Department of Pharmacology Medical, EA 1046, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>dopamine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>gait disorders</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>glutamate</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>noradrenaline</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>pharmacology</value></json:item></subject><articleId><json:string>FCP798</json:string></articleId><language><json:string>eng</json:string></language><abstract>Gait disorders form one component of the axial disorders observed in Parkinson’s disease (PD). Indeed, short steps with a forward‐leaning stance are diagnostic criteria for PD in the early stages of the condition. Gait disorders also represent a major source of therapeutic failure in the advanced stages of PD (with the appearance of freezing of gait and falls) because they do not respond optimally to the two hand late‐stage therapeutics – levodopa and electrical subthalamic nucleus (STN) stimulation. The late onset of doparesistance in these disorders may be linked to propagation of neurodegeneration to structures directly involved in gait control and to non‐dopaminergic neurotransmitter systems. The coeruleus locus (a source of noradrenaline) is rapidly and severely affected, leading to a major motor impact. The pedunculopontine nucleus (PPN) and lateral pontine tegmentum (rich in acetylcholine) are both involved in gait. Degenerative damage to the serotoninergic raphe nuclei appears to be less severe, although serotonin‐dopamine interactions are numerous and complex. Lastly, dopaminergic depletion leads to glutamatergic hyperactivity of the efferent pathways from the the STN to the PPN. However, the relationships between the various parkinsonian symptoms (and particularly gait disorders) and these pharmacological targets have yet to be fully elucidated. The goal of this review is to develop the various pathophysiological hypotheses published to date, in order to underpin and justify ongoing fundamental research and clinical trials in this disease area.</abstract><qualityIndicators><score>7.748</score><pdfVersion>1.3</pdfVersion><pdfPageSize>595.276 x 782.362 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>6</keywordCount><abstractCharCount>1580</abstractCharCount><pdfWordCount>8742</pdfWordCount><pdfCharCount>59918</pdfCharCount><pdfPageCount>15</pdfPageCount><abstractWordCount>229</abstractWordCount></qualityIndicators><title>Dopaminergic and non‐dopaminergic pharmacological hypotheses for gait disorders in Parkinson’s disease</title><genre><json:string>review-article</json:string></genre><host><volume>24</volume><publisherId><json:string>FCP</json:string></publisherId><pages><total>15</total><last>421</last><first>407</first></pages><issn><json:string>0767-3981</json:string></issn><issue>4</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1472-8206</json:string></eissn><title>Fundamental & Clinical Pharmacology</title><doi><json:string>10.1111/(ISSN)1472-8206</json:string></doi></host><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1111/j.1472-8206.2009.00798.x</json:string></doi><id>E30C8267F686573C916FD9B8D19D566FFA36D320</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/E30C8267F686573C916FD9B8D19D566FFA36D320/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/E30C8267F686573C916FD9B8D19D566FFA36D320/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/E30C8267F686573C916FD9B8D19D566FFA36D320/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Dopaminergic and non‐dopaminergic pharmacological hypotheses for gait disorders in Parkinson’s disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><availability><p>WILEY</p></availability><date>2010</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Dopaminergic and non‐dopaminergic pharmacological hypotheses for gait disorders in Parkinson’s disease</title><author><persName><forename type="first">David</forename><surname>Devos</surname></persName><note type="correspondence"><p>Correspondence and reprints:</p></note><affiliation>Department of Neurology and Movement Disorders, EA2683, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</affiliation></author><author><persName><forename type="first">L.</forename><surname>Defebvre</surname></persName><affiliation>Department of Neurology and Movement Disorders, EA2683, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</affiliation></author><author><persName><forename type="first">R.</forename><surname>Bordet</surname></persName><affiliation>Department of Pharmacology Medical, EA 1046, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</affiliation></author></analytic><monogr><title level="j">Fundamental & Clinical Pharmacology</title><idno type="pISSN">0767-3981</idno><idno type="eISSN">1472-8206</idno><idno type="DOI">10.1111/(ISSN)1472-8206</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2010-08"></date><biblScope unit="volume">24</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="407">407</biblScope><biblScope unit="page" to="421">421</biblScope></imprint></monogr><idno type="istex">E30C8267F686573C916FD9B8D19D566FFA36D320</idno><idno type="DOI">10.1111/j.1472-8206.2009.00798.x</idno><idno type="ArticleID">FCP798</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Gait disorders form one component of the axial disorders observed in Parkinson’s disease (PD). Indeed, short steps with a forward‐leaning stance are diagnostic criteria for PD in the early stages of the condition. Gait disorders also represent a major source of therapeutic failure in the advanced stages of PD (with the appearance of freezing of gait and falls) because they do not respond optimally to the two hand late‐stage therapeutics – levodopa and electrical subthalamic nucleus (STN) stimulation. The late onset of doparesistance in these disorders may be linked to propagation of neurodegeneration to structures directly involved in gait control and to non‐dopaminergic neurotransmitter systems. The coeruleus locus (a source of noradrenaline) is rapidly and severely affected, leading to a major motor impact. The pedunculopontine nucleus (PPN) and lateral pontine tegmentum (rich in acetylcholine) are both involved in gait. Degenerative damage to the serotoninergic raphe nuclei appears to be less severe, although serotonin‐dopamine interactions are numerous and complex. Lastly, dopaminergic depletion leads to glutamatergic hyperactivity of the efferent pathways from the the STN to the PPN. However, the relationships between the various parkinsonian symptoms (and particularly gait disorders) and these pharmacological targets have yet to be fully elucidated. The goal of this review is to develop the various pathophysiological hypotheses published to date, in order to underpin and justify ongoing fundamental research and clinical trials in this disease area.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>dopamine</term></item><item><term>gait disorders</term></item><item><term>glutamate</term></item><item><term>noradrenaline</term></item><item><term>Parkinson’s disease</term></item><item><term>pharmacology</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-08">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/E30C8267F686573C916FD9B8D19D566FFA36D320/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 Publishing Ltd</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1472-8206</doi><issn type="print">0767-3981</issn><issn type="electronic">1472-8206</issn><idGroup><id type="product" value="FCP"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="FUNDAMENTAL CLINICAL PHARMACOLOGY">Fundamental & Clinical Pharmacology</title></titleGroup></publicationMeta><publicationMeta level="part" position="08004"><doi origin="wiley">10.1111/fcp.2010.24.issue-4</doi><numberingGroup><numbering type="journalVolume" number="24">24</numbering><numbering type="journalIssue" number="4">4</numbering></numberingGroup><coverDate startDate="2010-08">August 2010</coverDate></publicationMeta><publicationMeta level="unit" type="reviewArticle" position="2" status="forIssue"><doi origin="wiley">10.1111/j.1472-8206.2009.00798.x</doi><idGroup><id type="unit" value="FCP798"></id></idGroup><countGroup><count type="pageTotal" number="15"></count></countGroup><titleGroup><title type="tocHeading1">REVIEW ARTICLES</title></titleGroup><copyright>© 2010 The Authors Journal compilation © 2010 Société Française de Pharmacologie et de Thérapeutique</copyright><eventGroup><event type="firstOnline" date="2010-02-12"></event><event type="publishedOnlineFinalForm" date="2010-07-06"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.15 mode:FullText source:FullText result:FullText" date="2010-07-21"></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="407">407</numbering><numbering type="pageLast" number="421">421</numbering></numberingGroup><correspondenceTo> Correspondence and reprints: <email normalForm="d-devos@chru-lille.fr">d‐devos@chru‐lille.fr</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:FCP.FCP798.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received 4 June 2009; received 8 September 2009; accepted 14 October 2009</unparsedEditorialHistory><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="1"></count></countGroup><titleGroup><title type="main">Dopaminergic and non‐dopaminergic pharmacological hypotheses for gait disorders in Parkinson’s disease</title><title type="shortAuthors">D. Devos <i>et al.</i></title><title type="short"><i>Pharmacology of parkinsonian gait disorders</i></title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1" corresponding="yes"><personName><givenNames>David</givenNames><familyName>Devos</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>L.</givenNames><familyName>Defebvre</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a2"><personName><givenNames>R.</givenNames><familyName>Bordet</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="FR"><unparsedAffiliation>Department of Neurology and Movement Disorders, EA2683, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="FR"><unparsedAffiliation>Department of Pharmacology Medical, EA 1046, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">dopamine</keyword><keyword xml:id="k2">gait disorders</keyword><keyword xml:id="k3">glutamate</keyword><keyword xml:id="k4">noradrenaline</keyword><keyword xml:id="k5">Parkinson’s disease</keyword><keyword xml:id="k6">pharmacology</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Gait disorders form one component of the axial disorders observed in Parkinson’s disease (PD). Indeed, short steps with a forward‐leaning stance are diagnostic criteria for PD in the early stages of the condition. Gait disorders also represent a major source of therapeutic failure in the advanced stages of PD (with the appearance of freezing of gait and falls) because they do not respond optimally to the two hand late‐stage therapeutics – levodopa and electrical subthalamic nucleus (STN) stimulation. The late onset of doparesistance in these disorders may be linked to propagation of neurodegeneration to structures directly involved in gait control and to non‐dopaminergic neurotransmitter systems. The coeruleus locus (a source of noradrenaline) is rapidly and severely affected, leading to a major motor impact. The pedunculopontine nucleus (PPN) and lateral pontine tegmentum (rich in acetylcholine) are both involved in gait. Degenerative damage to the serotoninergic raphe nuclei appears to be less severe, although serotonin‐dopamine interactions are numerous and complex. Lastly, dopaminergic depletion leads to glutamatergic hyperactivity of the efferent pathways from the the STN to the PPN. However, the relationships between the various parkinsonian symptoms (and particularly gait disorders) and these pharmacological targets have yet to be fully elucidated. The goal of this review is to develop the various pathophysiological hypotheses published to date, in order to underpin and justify ongoing fundamental research and clinical trials in this disease area.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Dopaminergic and non‐dopaminergic pharmacological hypotheses for gait disorders in Parkinson’s disease</title></titleInfo><titleInfo type="abbreviated"><title>Pharmacology of parkinsonian gait disorders</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Dopaminergic and non‐dopaminergic pharmacological hypotheses for gait disorders in Parkinson’s disease</title></titleInfo><name type="personal"><namePart type="given">David</namePart><namePart type="family">Devos</namePart><affiliation>Department of Neurology and Movement Disorders, EA2683, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</affiliation><description>Correspondence and reprints: </description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L.</namePart><namePart type="family">Defebvre</namePart><affiliation>Department of Neurology and Movement Disorders, EA2683, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.</namePart><namePart type="family">Bordet</namePart><affiliation>Department of Pharmacology Medical, EA 1046, IMPRT, IFR 114, Faculty of Medicine Lille 2, University of Lille Nord de France, Lille University Hospital, Lille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="review-article" displayLabel="reviewArticle"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2010-08</dateIssued><edition>Received 4 June 2009; received 8 September 2009; accepted 14 October 2009</edition><copyrightDate encoding="w3cdtf">2010</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="tables">1</extent></physicalDescription><abstract lang="en">Gait disorders form one component of the axial disorders observed in Parkinson’s disease (PD). Indeed, short steps with a forward‐leaning stance are diagnostic criteria for PD in the early stages of the condition. Gait disorders also represent a major source of therapeutic failure in the advanced stages of PD (with the appearance of freezing of gait and falls) because they do not respond optimally to the two hand late‐stage therapeutics – levodopa and electrical subthalamic nucleus (STN) stimulation. The late onset of doparesistance in these disorders may be linked to propagation of neurodegeneration to structures directly involved in gait control and to non‐dopaminergic neurotransmitter systems. The coeruleus locus (a source of noradrenaline) is rapidly and severely affected, leading to a major motor impact. The pedunculopontine nucleus (PPN) and lateral pontine tegmentum (rich in acetylcholine) are both involved in gait. Degenerative damage to the serotoninergic raphe nuclei appears to be less severe, although serotonin‐dopamine interactions are numerous and complex. Lastly, dopaminergic depletion leads to glutamatergic hyperactivity of the efferent pathways from the the STN to the PPN. However, the relationships between the various parkinsonian symptoms (and particularly gait disorders) and these pharmacological targets have yet to be fully elucidated. The goal of this review is to develop the various pathophysiological hypotheses published to date, in order to underpin and justify ongoing fundamental research and clinical trials in this disease area.</abstract><subject lang="en"><genre>Keywords</genre><topic>dopamine</topic><topic>gait disorders</topic><topic>glutamate</topic><topic>noradrenaline</topic><topic>Parkinson’s disease</topic><topic>pharmacology</topic></subject><relatedItem type="host"><titleInfo><title>Fundamental & Clinical Pharmacology</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0767-3981</identifier><identifier type="eISSN">1472-8206</identifier><identifier type="DOI">10.1111/(ISSN)1472-8206</identifier><identifier type="PublisherID">FCP</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>24</number></detail><detail type="issue"><caption>no.</caption><number>4</number></detail><extent unit="pages"><start>407</start><end>421</end><total>15</total></extent></part></relatedItem><identifier type="istex">E30C8267F686573C916FD9B8D19D566FFA36D320</identifier><identifier type="DOI">10.1111/j.1472-8206.2009.00798.x</identifier><identifier type="ArticleID">FCP798</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2010 The Authors Journal compilation © 2010 Société Française de Pharmacologie et de Thérapeutique</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Publishing 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 000582 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 000582 | 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:E30C8267F686573C916FD9B8D19D566FFA36D320
|texte= Dopaminergic and non‐dopaminergic pharmacological hypotheses for gait disorders in Parkinson’s disease
}}
| This area was generated with Dilib version V0.6.23. |  |