Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease
Identifieur interne : 000485 ( Pmc/Corpus ); précédent : 000484; suivant : 000486Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease
Auteurs : Carine Karachi ; David Grabli ; Frédéric A. Bernard ; Dominique Tandé ; Nicolas Wattiez ; Hayat Belaid ; Eric Bardinet ; Annick Prigent ; Hans-Peter Nothacker ; Stéphane Hunot ; Andreas Hartmann ; Stéphane Lehéricy ; Etienne C. Hirsch ; Chantal FrançoisSource :
- The Journal of Clinical Investigation [ 0021-9738 ] ; 2010.
Abstract
Gait disorders and postural instability, which are commonly observed in elderly patients with Parkinson disease (PD), respond poorly to dopaminergic agents used to treat other parkinsonian symptoms. The brain structures underlying gait disorders and falls in PD and aging remain to be characterized. Using functional MRI in healthy human subjects, we have shown here that activity of the mesencephalic locomotor region (MLR), which is composed of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus, was modulated by the speed of imagined gait, with faster imagined gait activating a discrete cluster within the MLR. Furthermore, the presence of gait disorders in patients with PD and in aged monkeys rendered parkinsonian by MPTP intoxication correlated with loss of PPN cholinergic neurons. Bilateral lesioning of the cholinergic part of the PPN induced gait and postural deficits in nondopaminergic lesioned monkeys. Our data therefore reveal that the cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD.
Url:
DOI: 10.1172/JCI42642
PubMed: 20628197
PubMed Central: 2912198
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PMC:2912198Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease</title><author><name sortKey="Karachi, Carine" sort="Karachi, Carine" uniqKey="Karachi C" first="Carine" last="Karachi">Carine Karachi</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">Assistance Publique-Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Grabli, David" sort="Grabli, David" uniqKey="Grabli D" first="David" last="Grabli">David Grabli</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">Assistance Publique-Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Bernard, Frederic A" sort="Bernard, Frederic A" uniqKey="Bernard F" first="Frédéric A." last="Bernard">Frédéric A. Bernard</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">Laboratoire d’Imagerie et de Neurosciences Cognitives, FRE 3289, CNRS/Université de Strasbourg, Strasbourg, France.</nlm:aff></affiliation></author><author><name sortKey="Tande, Dominique" sort="Tande, Dominique" uniqKey="Tande D" first="Dominique" last="Tandé">Dominique Tandé</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Wattiez, Nicolas" sort="Wattiez, Nicolas" uniqKey="Wattiez N" first="Nicolas" last="Wattiez">Nicolas Wattiez</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Belaid, Hayat" sort="Belaid, Hayat" uniqKey="Belaid H" first="Hayat" last="Belaid">Hayat Belaid</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">Assistance Publique-Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Bardinet, Eric" sort="Bardinet, Eric" uniqKey="Bardinet E" first="Eric" last="Bardinet">Eric Bardinet</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Prigent, Annick" sort="Prigent, Annick" uniqKey="Prigent A" first="Annick" last="Prigent">Annick Prigent</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Nothacker, Hans Peter" sort="Nothacker, Hans Peter" uniqKey="Nothacker H" first="Hans-Peter" last="Nothacker">Hans-Peter Nothacker</name><affiliation><nlm:aff id="JCI42642">Department of Pharmacology, School of Medicine, University of California, Irvine, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">Assistance Publique-Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Lehericy, Stephane" sort="Lehericy, Stephane" uniqKey="Lehericy S" first="Stéphane" last="Lehéricy">Stéphane Lehéricy</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Francois, Chantal" sort="Francois, Chantal" uniqKey="Francois C" first="Chantal" last="François">Chantal François</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20628197</idno><idno type="pmc">2912198</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912198</idno><idno type="RBID">PMC:2912198</idno><idno type="doi">10.1172/JCI42642</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000485</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000485</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease</title><author><name sortKey="Karachi, Carine" sort="Karachi, Carine" uniqKey="Karachi C" first="Carine" last="Karachi">Carine Karachi</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">Assistance Publique-Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Grabli, David" sort="Grabli, David" uniqKey="Grabli D" first="David" last="Grabli">David Grabli</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">Assistance Publique-Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Bernard, Frederic A" sort="Bernard, Frederic A" uniqKey="Bernard F" first="Frédéric A." last="Bernard">Frédéric A. Bernard</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">Laboratoire d’Imagerie et de Neurosciences Cognitives, FRE 3289, CNRS/Université de Strasbourg, Strasbourg, France.</nlm:aff></affiliation></author><author><name sortKey="Tande, Dominique" sort="Tande, Dominique" uniqKey="Tande D" first="Dominique" last="Tandé">Dominique Tandé</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Wattiez, Nicolas" sort="Wattiez, Nicolas" uniqKey="Wattiez N" first="Nicolas" last="Wattiez">Nicolas Wattiez</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Belaid, Hayat" sort="Belaid, Hayat" uniqKey="Belaid H" first="Hayat" last="Belaid">Hayat Belaid</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">Assistance Publique-Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Bardinet, Eric" sort="Bardinet, Eric" uniqKey="Bardinet E" first="Eric" last="Bardinet">Eric Bardinet</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Prigent, Annick" sort="Prigent, Annick" uniqKey="Prigent A" first="Annick" last="Prigent">Annick Prigent</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Nothacker, Hans Peter" sort="Nothacker, Hans Peter" uniqKey="Nothacker H" first="Hans-Peter" last="Nothacker">Hans-Peter Nothacker</name><affiliation><nlm:aff id="JCI42642">Department of Pharmacology, School of Medicine, University of California, Irvine, California, USA.</nlm:aff></affiliation></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">Assistance Publique-Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Lehericy, Stephane" sort="Lehericy, Stephane" uniqKey="Lehericy S" first="Stéphane" last="Lehéricy">Stéphane Lehéricy</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author><author><name sortKey="Francois, Chantal" sort="Francois, Chantal" uniqKey="Francois C" first="Chantal" last="François">Chantal François</name><affiliation><nlm:aff id="JCI42642">Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">INSERM, U975, Paris, France.</nlm:aff></affiliation><affiliation><nlm:aff id="JCI42642">CNRS, UMR 7225, Paris, France.</nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Clinical Investigation</title><idno type="ISSN">0021-9738</idno><idno type="eISSN">1558-8238</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Gait disorders and postural instability, which are commonly observed in elderly patients with Parkinson disease (PD), respond poorly to dopaminergic agents used to treat other parkinsonian symptoms. The brain structures underlying gait disorders and falls in PD and aging remain to be characterized. Using functional MRI in healthy human subjects, we have shown here that activity of the mesencephalic locomotor region (MLR), which is composed of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus, was modulated by the speed of imagined gait, with faster imagined gait activating a discrete cluster within the MLR. Furthermore, the presence of gait disorders in patients with PD and in aged monkeys rendered parkinsonian by MPTP intoxication correlated with loss of PPN cholinergic neurons. Bilateral lesioning of the cholinergic part of the PPN induced gait and postural deficits in nondopaminergic lesioned monkeys. Our data therefore reveal that the cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Invest</journal-id><journal-id journal-id-type="publisher-id">J CLIN INVEST</journal-id><journal-title-group><journal-title>The Journal of Clinical Investigation</journal-title></journal-title-group><issn pub-type="ppub">0021-9738</issn><issn pub-type="epub">1558-8238</issn><publisher><publisher-name>American Society for Clinical Investigation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20628197</article-id><article-id pub-id-type="pmc">2912198</article-id><article-id pub-id-type="publisher-id">42642</article-id><article-id pub-id-type="doi">10.1172/JCI42642</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Karachi</surname><given-names>Carine</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref><xref ref-type="aff" rid="JCI42642">4</xref></contrib><contrib contrib-type="author"><name><surname>Grabli</surname><given-names>David</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref><xref ref-type="aff" rid="JCI42642">4</xref></contrib><contrib contrib-type="author"><name><surname>Bernard</surname><given-names>Frédéric A.</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref><xref ref-type="aff" rid="JCI42642">5</xref></contrib><contrib contrib-type="author"><name><surname>Tandé</surname><given-names>Dominique</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref></contrib><contrib contrib-type="author"><name><surname>Wattiez</surname><given-names>Nicolas</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref></contrib><contrib contrib-type="author"><name><surname>Belaid</surname><given-names>Hayat</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref><xref ref-type="aff" rid="JCI42642">4</xref></contrib><contrib contrib-type="author"><name><surname>Bardinet</surname><given-names>Eric</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref></contrib><contrib contrib-type="author"><name><surname>Prigent</surname><given-names>Annick</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref></contrib><contrib contrib-type="author"><name><surname>Nothacker</surname><given-names>Hans-Peter</given-names></name><xref ref-type="aff" rid="JCI42642">6</xref></contrib><contrib contrib-type="author"><name><surname>Hunot</surname><given-names>Stéphane</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref></contrib><contrib contrib-type="author"><name><surname>Hartmann</surname><given-names>Andreas</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref><xref ref-type="aff" rid="JCI42642">4</xref></contrib><contrib contrib-type="author"><name><surname>Lehéricy</surname><given-names>Stéphane</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref></contrib><contrib contrib-type="author"><name><surname>Hirsch</surname><given-names>Etienne C.</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref></contrib><contrib contrib-type="author"><name><surname>François</surname><given-names>Chantal</given-names></name><xref ref-type="aff" rid="JCI42642">1</xref><xref ref-type="aff" rid="JCI42642">2</xref><xref ref-type="aff" rid="JCI42642">3</xref></contrib></contrib-group><aff id="JCI42642"><label>1</label>Université Pierre et Marie Curie — Paris 6, CR-ICM, UMR-S975, Paris, France.<label>2</label>INSERM, U975, Paris, France.<label>3</label>CNRS, UMR 7225, Paris, France.<label>4</label>Assistance Publique-Hôpitaux de Paris, Groupe Pitié-Salpêtrière, Paris, France.<label>5</label>Laboratoire d’Imagerie et de Neurosciences Cognitives, FRE 3289, CNRS/Université de Strasbourg, Strasbourg, France.<label>6</label>Department of Pharmacology, School of Medicine, University of California, Irvine, California, USA.</aff><author-notes><corresp>Address correspondence to: Chantal François or Etienne C. Hirsch, GH Pitié Salpêtrière, 4ème étage, 47 Boulevard de l’Hôpital, 75651 Paris Cedex 13, France. Phone: 33.1.42.16.00.68; Fax: 33.1.45.82.88.93; E-mail:
<email>chantal.francois@upmc.fr</email> (C. François). Phone: 33.1.42.16.22.02; Fax: 33.1.44.24.36.58; E-mail:
<email>Etienne.hirsch@upmc.fr</email> (E.C. Hirsch).
</corresp><fn><p><bold>Authorship note:</bold> Carine Karachi and David Grabli contributed equally to this work.
</p></fn></author-notes><pub-date pub-type="epub"><day>12</day><month>7</month><year>2010</year></pub-date><pub-date pub-type="ppub"><day>2</day><month>8</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>12</day><month>7</month><year>2010</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>120</volume><issue>8</issue><fpage>2745</fpage><lpage>2754</lpage><history><date date-type="received"><day>11</day><month>2</month><year>2010</year></date><date date-type="accepted"><day>26</day><month>5</month><year>2010</year></date></history><permissions><copyright-statement>Copyright © 2010, American Society for Clinical Investigation</copyright-statement></permissions><abstract><p>Gait disorders and postural instability, which are commonly observed in elderly patients with Parkinson disease (PD), respond poorly to dopaminergic agents used to treat other parkinsonian symptoms. The brain structures underlying gait disorders and falls in PD and aging remain to be characterized. Using functional MRI in healthy human subjects, we have shown here that activity of the mesencephalic locomotor region (MLR), which is composed of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus, was modulated by the speed of imagined gait, with faster imagined gait activating a discrete cluster within the MLR. Furthermore, the presence of gait disorders in patients with PD and in aged monkeys rendered parkinsonian by MPTP intoxication correlated with loss of PPN cholinergic neurons. Bilateral lesioning of the cholinergic part of the PPN induced gait and postural deficits in nondopaminergic lesioned monkeys. Our data therefore reveal that the cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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