Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease.
Identifieur interne : 000A70 ( PubMed/Corpus ); précédent : 000A69; suivant : 000A71Cholinergic 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 [ 1558-8238 ] ; 2010.
English descriptors
- KwdEn :
- MESH :
- physiology : Parasympathetic Nervous System, Pedunculopontine Tegmental Nucleus.
- physiopathology : MPTP Poisoning, Parkinson Disease.
- Accidental Falls, Adult, Aged, Aged, 80 and over, Animals, Female, Gait, Humans, Macaca, Male, Postural Balance.
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.
DOI: 10.1172/JCI42642
PubMed: 20628197
Links to Exploration step
pubmed:20628197Le document en format XML
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Bernard</name></author><author><name sortKey="Tande, Dominique" sort="Tande, Dominique" uniqKey="Tande D" first="Dominique" last="Tandé">Dominique Tandé</name></author><author><name sortKey="Wattiez, Nicolas" sort="Wattiez, Nicolas" uniqKey="Wattiez N" first="Nicolas" last="Wattiez">Nicolas Wattiez</name></author><author><name sortKey="Belaid, Hayat" sort="Belaid, Hayat" uniqKey="Belaid H" first="Hayat" last="Belaid">Hayat Belaid</name></author><author><name sortKey="Bardinet, Eric" sort="Bardinet, Eric" uniqKey="Bardinet E" first="Eric" last="Bardinet">Eric Bardinet</name></author><author><name sortKey="Prigent, Annick" sort="Prigent, Annick" uniqKey="Prigent A" first="Annick" last="Prigent">Annick Prigent</name></author><author><name sortKey="Nothacker, Hans Peter" sort="Nothacker, Hans Peter" uniqKey="Nothacker H" first="Hans-Peter" last="Nothacker">Hans-Peter Nothacker</name></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name></author><author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name></author><author><name sortKey="Lehericy, Stephane" sort="Lehericy, Stephane" uniqKey="Lehericy S" first="Stéphane" last="Lehéricy">Stéphane Lehéricy</name></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C" last="Hirsch">Etienne C. 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Bernard</name></author><author><name sortKey="Tande, Dominique" sort="Tande, Dominique" uniqKey="Tande D" first="Dominique" last="Tandé">Dominique Tandé</name></author><author><name sortKey="Wattiez, Nicolas" sort="Wattiez, Nicolas" uniqKey="Wattiez N" first="Nicolas" last="Wattiez">Nicolas Wattiez</name></author><author><name sortKey="Belaid, Hayat" sort="Belaid, Hayat" uniqKey="Belaid H" first="Hayat" last="Belaid">Hayat Belaid</name></author><author><name sortKey="Bardinet, Eric" sort="Bardinet, Eric" uniqKey="Bardinet E" first="Eric" last="Bardinet">Eric Bardinet</name></author><author><name sortKey="Prigent, Annick" sort="Prigent, Annick" uniqKey="Prigent A" first="Annick" last="Prigent">Annick Prigent</name></author><author><name sortKey="Nothacker, Hans Peter" sort="Nothacker, Hans Peter" uniqKey="Nothacker H" first="Hans-Peter" last="Nothacker">Hans-Peter Nothacker</name></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name></author><author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name></author><author><name sortKey="Lehericy, Stephane" sort="Lehericy, Stephane" uniqKey="Lehericy S" first="Stéphane" last="Lehéricy">Stéphane Lehéricy</name></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C" last="Hirsch">Etienne C. Hirsch</name></author><author><name sortKey="Francois, Chantal" sort="Francois, Chantal" uniqKey="Francois C" first="Chantal" last="François">Chantal François</name></author></analytic><series><title level="j">The Journal of clinical investigation</title><idno type="eISSN">1558-8238</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Accidental Falls</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Female</term><term>Gait</term><term>Humans</term><term>MPTP Poisoning (physiopathology)</term><term>Macaca</term><term>Male</term><term>Parasympathetic Nervous System (physiology)</term><term>Parkinson Disease (physiopathology)</term><term>Pedunculopontine Tegmental Nucleus (physiology)</term><term>Postural Balance</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Parasympathetic Nervous System</term><term>Pedunculopontine Tegmental Nucleus</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>MPTP Poisoning</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Accidental Falls</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Female</term><term>Gait</term><term>Humans</term><term>Macaca</term><term>Male</term><term>Postural Balance</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20628197</PMID><DateCreated><Year>2010</Year><Month>08</Month><Day>03</Day></DateCreated><DateCompleted><Year>2010</Year><Month>09</Month><Day>02</Day></DateCompleted><DateRevised><Year>2014</Year><Month>12</Month><Day>03</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1558-8238</ISSN><JournalIssue CitedMedium="Internet"><Volume>120</Volume><Issue>8</Issue><PubDate><Year>2010</Year><Month>Aug</Month></PubDate></JournalIssue><Title>The Journal of clinical investigation</Title><ISOAbbreviation>J. Clin. Invest.</ISOAbbreviation></Journal><ArticleTitle>Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease.</ArticleTitle><Pagination><MedlinePgn>2745-54</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1172/JCI42642</ELocationID><ELocationID EIdType="pii" ValidYN="Y">42642</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Karachi</LastName><ForeName>Carine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Université Pierre et Marie Curie -Paris 6, CR-ICM, UMR-S975, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Grabli</LastName><ForeName>David</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Bernard</LastName><ForeName>Frédéric A</ForeName><Initials>FA</Initials></Author><Author ValidYN="Y"><LastName>Tandé</LastName><ForeName>Dominique</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Wattiez</LastName><ForeName>Nicolas</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Belaid</LastName><ForeName>Hayat</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Bardinet</LastName><ForeName>Eric</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Prigent</LastName><ForeName>Annick</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Nothacker</LastName><ForeName>Hans-Peter</ForeName><Initials>HP</Initials></Author><Author ValidYN="Y"><LastName>Hunot</LastName><ForeName>Stéphane</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Hartmann</LastName><ForeName>Andreas</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Lehéricy</LastName><ForeName>Stéphane</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Hirsch</LastName><ForeName>Etienne C</ForeName><Initials>EC</Initials></Author><Author ValidYN="Y"><LastName>François</LastName><ForeName>Chantal</ForeName><Initials>C</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2010</Year><Month>07</Month><Day>12</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Clin Invest</MedlineTA><NlmUniqueID>7802877</NlmUniqueID><ISSNLinking>0021-9738</ISSNLinking></MedlineJournalInfo><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Neuroscience. 1984 Jul;12(3):669-86</RefSource><PMID Version="1">6382047</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Neuropsychologia. 1971 Mar;9(1):97-113</RefSource><PMID 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Aug;17(2-3):69-88</RefSource><PMID Version="1">3093780</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000058" MajorTopicYN="N">Accidental Falls</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005684" MajorTopicYN="Y">Gait</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020267" MajorTopicYN="N">MPTP Poisoning</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008251" MajorTopicYN="N">Macaca</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010275" MajorTopicYN="N">Parasympathetic Nervous System</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045042" MajorTopicYN="N">Pedunculopontine Tegmental Nucleus</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004856" MajorTopicYN="Y">Postural Balance</DescriptorName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC2912198</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2010</Year><Month>02</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2010</Year><Month>05</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>7</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>7</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>9</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">20628197</ArticleId><ArticleId IdType="pii">42642</ArticleId><ArticleId IdType="doi">10.1172/JCI42642</ArticleId><ArticleId 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