Role of pedunculopontine cholinergic neurons in the vulnerability of nigral dopaminergic neurons in Parkinson's disease.
Identifieur interne : 000217 ( PubMed/Corpus ); précédent : 000216; suivant : 000218Role of pedunculopontine cholinergic neurons in the vulnerability of nigral dopaminergic neurons in Parkinson's disease.
Auteurs : Manale Bensaid ; Patrick P. Michel ; Stewart D. Clark ; Etienne C. Hirsch ; Chantal FrançoisSource :
- Experimental neurology [ 1090-2430 ] ; 2016.
English descriptors
- KwdEn :
- MESH :
- chemical : Oxidopamine.
- pathology : Cholinergic Neurons, Dopaminergic Neurons, Parkinson Disease, Pedunculopontine Tegmental Nucleus, Substantia Nigra.
- Animals, Macaca fascicularis, Male, Rats, Rats, Sprague-Dawley.
Abstract
Pedunculopontine nucleus (PPN) cholinergic neurons, which exert excitatory nicotinic control over substantia nigra dopaminergic neurons, degenerate in Parkinson's disease (PD). This finding and other studies showing that nicotine, the preferential agonist of nicotinic acetylcholine receptors, is neuroprotective in experimental models of PD suggest that a deficit in PPN excitatory cholinergic inputs might contribute to the death of nigral dopaminergic neurons in PD. To explore this possibility, we used lesion paradigms of dopaminergic and/or cholinergic systems in rats and monkeys. Consistent with our hypothesis, we observed that stereotaxic lesioning of PPN cholinergic neurons with diphtheria toxin coupled to urotensin II resulted in a significant loss of nigral dopaminergic neurons in rats and induced morphological changes in these neurons in macaques. Unexpectedly, a lesion of dopaminergic neurons induced by unilateral striatal injection of 6-hydroxydopamine (6-OHDA) in rats, or by repeated systemic injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in macaques, led to a 29% and 7% loss of PPN cholinergic neurons, respectively. Lastly, when the PPN cholinergic lesion was performed in rats in which the dopaminergic lesion induced by 6-OHDA was in progress, loss of cholinergic neurons was more drastic than when each neurotransmitter system was lesioned separately. Thus, our results suggest that strong PPN cholinergic and dopaminergic interactions may be an important mechanism in the pathophysiology of PD.
DOI: 10.1016/j.expneurol.2015.11.004
PubMed: 26571193
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pubmed:26571193Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Role of pedunculopontine cholinergic neurons in the vulnerability of nigral dopaminergic neurons in Parkinson's disease.</title><author><name sortKey="Bensaid, Manale" sort="Bensaid, Manale" uniqKey="Bensaid M" first="Manale" last="Bensaid">Manale Bensaid</name><affiliation><nlm:affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, ICM, F-75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P" last="Michel">Patrick P. Michel</name><affiliation><nlm:affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, ICM, F-75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Clark, Stewart D" sort="Clark, Stewart D" uniqKey="Clark S" first="Stewart D" last="Clark">Stewart D. Clark</name><affiliation><nlm:affiliation>Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York 14214, United States.</nlm:affiliation></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:affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, ICM, F-75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Francois, Chantal" sort="Francois, Chantal" uniqKey="Francois C" first="Chantal" last="François">Chantal François</name><affiliation><nlm:affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, ICM, F-75013 Paris, France. Electronic address: Chantal.francois@upmc.fr.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26571193</idno><idno type="pmid">26571193</idno><idno type="doi">10.1016/j.expneurol.2015.11.004</idno><idno type="wicri:Area/PubMed/Corpus">000217</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000217</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Role of pedunculopontine cholinergic neurons in the vulnerability of nigral dopaminergic neurons in Parkinson's disease.</title><author><name sortKey="Bensaid, Manale" sort="Bensaid, Manale" uniqKey="Bensaid M" first="Manale" last="Bensaid">Manale Bensaid</name><affiliation><nlm:affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, ICM, F-75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P" last="Michel">Patrick P. Michel</name><affiliation><nlm:affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, ICM, F-75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Clark, Stewart D" sort="Clark, Stewart D" uniqKey="Clark S" first="Stewart D" last="Clark">Stewart D. Clark</name><affiliation><nlm:affiliation>Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York 14214, United States.</nlm:affiliation></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:affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, ICM, F-75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Francois, Chantal" sort="Francois, Chantal" uniqKey="Francois C" first="Chantal" last="François">Chantal François</name><affiliation><nlm:affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, ICM, F-75013 Paris, France. Electronic address: Chantal.francois@upmc.fr.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Experimental neurology</title><idno type="eISSN">1090-2430</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cholinergic Neurons (pathology)</term><term>Dopaminergic Neurons (pathology)</term><term>Macaca fascicularis</term><term>Male</term><term>Oxidopamine</term><term>Parkinson Disease (pathology)</term><term>Pedunculopontine Tegmental Nucleus (pathology)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Substantia Nigra (pathology)</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Oxidopamine</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Cholinergic Neurons</term><term>Dopaminergic Neurons</term><term>Parkinson Disease</term><term>Pedunculopontine Tegmental Nucleus</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Macaca fascicularis</term><term>Male</term><term>Rats</term><term>Rats, Sprague-Dawley</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Pedunculopontine nucleus (PPN) cholinergic neurons, which exert excitatory nicotinic control over substantia nigra dopaminergic neurons, degenerate in Parkinson's disease (PD). This finding and other studies showing that nicotine, the preferential agonist of nicotinic acetylcholine receptors, is neuroprotective in experimental models of PD suggest that a deficit in PPN excitatory cholinergic inputs might contribute to the death of nigral dopaminergic neurons in PD. To explore this possibility, we used lesion paradigms of dopaminergic and/or cholinergic systems in rats and monkeys. Consistent with our hypothesis, we observed that stereotaxic lesioning of PPN cholinergic neurons with diphtheria toxin coupled to urotensin II resulted in a significant loss of nigral dopaminergic neurons in rats and induced morphological changes in these neurons in macaques. Unexpectedly, a lesion of dopaminergic neurons induced by unilateral striatal injection of 6-hydroxydopamine (6-OHDA) in rats, or by repeated systemic injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in macaques, led to a 29% and 7% loss of PPN cholinergic neurons, respectively. Lastly, when the PPN cholinergic lesion was performed in rats in which the dopaminergic lesion induced by 6-OHDA was in progress, loss of cholinergic neurons was more drastic than when each neurotransmitter system was lesioned separately. Thus, our results suggest that strong PPN cholinergic and dopaminergic interactions may be an important mechanism in the pathophysiology of PD.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26571193</PMID><DateCreated><Year>2015</Year><Month>12</Month><Day>22</Day></DateCreated><DateCompleted><Year>2016</Year><Month>04</Month><Day>29</Day></DateCompleted><DateRevised><Year>2015</Year><Month>12</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1090-2430</ISSN><JournalIssue CitedMedium="Internet"><Volume>275 Pt 1</Volume><PubDate><Year>2016</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Experimental neurology</Title><ISOAbbreviation>Exp. Neurol.</ISOAbbreviation></Journal><ArticleTitle>Role of pedunculopontine cholinergic neurons in the vulnerability of nigral dopaminergic neurons in Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>209-19</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.expneurol.2015.11.004</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0014-4886(15)30118-7</ELocationID><Abstract><AbstractText>Pedunculopontine nucleus (PPN) cholinergic neurons, which exert excitatory nicotinic control over substantia nigra dopaminergic neurons, degenerate in Parkinson's disease (PD). This finding and other studies showing that nicotine, the preferential agonist of nicotinic acetylcholine receptors, is neuroprotective in experimental models of PD suggest that a deficit in PPN excitatory cholinergic inputs might contribute to the death of nigral dopaminergic neurons in PD. To explore this possibility, we used lesion paradigms of dopaminergic and/or cholinergic systems in rats and monkeys. Consistent with our hypothesis, we observed that stereotaxic lesioning of PPN cholinergic neurons with diphtheria toxin coupled to urotensin II resulted in a significant loss of nigral dopaminergic neurons in rats and induced morphological changes in these neurons in macaques. Unexpectedly, a lesion of dopaminergic neurons induced by unilateral striatal injection of 6-hydroxydopamine (6-OHDA) in rats, or by repeated systemic injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in macaques, led to a 29% and 7% loss of PPN cholinergic neurons, respectively. Lastly, when the PPN cholinergic lesion was performed in rats in which the dopaminergic lesion induced by 6-OHDA was in progress, loss of cholinergic neurons was more drastic than when each neurotransmitter system was lesioned separately. Thus, our results suggest that strong PPN cholinergic and dopaminergic interactions may be an important mechanism in the pathophysiology of PD.</AbstractText><CopyrightInformation>Copyright © 2015 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bensaid</LastName><ForeName>Manale</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, ICM, F-75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Michel</LastName><ForeName>Patrick P</ForeName><Initials>PP</Initials><AffiliationInfo><Affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, ICM, F-75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Clark</LastName><ForeName>Stewart D</ForeName><Initials>SD</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York 14214, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hirsch</LastName><ForeName>Etienne C</ForeName><Initials>EC</Initials><AffiliationInfo><Affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, ICM, F-75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>François</LastName><ForeName>Chantal</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, ICM, F-75013 Paris, France. Electronic address: Chantal.francois@upmc.fr.</Affiliation></AffiliationInfo></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>2015</Year><Month>11</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Exp Neurol</MedlineTA><NlmUniqueID>0370712</NlmUniqueID><ISSNLinking>0014-4886</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>8HW4YBZ748</RegistryNumber><NameOfSubstance UI="D016627">Oxidopamine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059329" MajorTopicYN="N">Cholinergic Neurons</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059290" MajorTopicYN="N">Dopaminergic Neurons</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008252" MajorTopicYN="N">Macaca fascicularis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016627" MajorTopicYN="N">Oxidopamine</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045042" MajorTopicYN="N">Pedunculopontine Tegmental Nucleus</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013378" MajorTopicYN="N">Substantia Nigra</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">6-OHDA</Keyword><Keyword MajorTopicYN="N">Cholinergic</Keyword><Keyword MajorTopicYN="N">Diphtheria toxin-urotensin II</Keyword><Keyword MajorTopicYN="N">Dopamine</Keyword><Keyword MajorTopicYN="N">MPTP</Keyword><Keyword MajorTopicYN="N">Parkinson's disease</Keyword><Keyword MajorTopicYN="N">Pedunculopontine nucleus</Keyword><Keyword MajorTopicYN="N">Substantia nigra</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>08</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2015</Year><Month>10</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>11</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>11</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>11</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>4</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26571193</ArticleId><ArticleId IdType="pii">S0014-4886(15)30118-7</ArticleId><ArticleId IdType="doi">10.1016/j.expneurol.2015.11.004</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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