5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease.
Identifieur interne : 000E09 ( PubMed/Checkpoint ); précédent : 000E08; suivant : 000E105-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease.
Auteurs : Erwan Bezard [France] ; Irene Gerlach ; Rosario Moratalla ; Christian E. Gross ; Reinhard JorkSource :
- Neurobiology of disease [ 0969-9961 ] ; 2006.
English descriptors
- KwdEn :
- Animals, Benzopyrans (therapeutic use), Brain (drug effects), Brain (pathology), In Situ Hybridization, Macaca, Male, Mice, Mice, Inbred C57BL, Nerve Degeneration (drug therapy), Nerve Degeneration (pathology), Neurons (drug effects), Neurons (pathology), Neuroprotective Agents (therapeutic use), Parkinsonian Disorders (prevention & control), Receptor, Serotonin, 5-HT1A (drug effects), Receptor, Serotonin, 5-HT1A (metabolism), Serotonin Receptor Agonists (therapeutic use), Thiazoles (therapeutic use), Tyrosine 3-Monooxygenase (drug effects), Tyrosine 3-Monooxygenase (metabolism).
- MESH :
- chemical , drug effects : Receptor, Serotonin, 5-HT1A, Tyrosine 3-Monooxygenase.
- chemical , metabolism : Receptor, Serotonin, 5-HT1A, Tyrosine 3-Monooxygenase.
- chemical , therapeutic use : Benzopyrans, Neuroprotective Agents, Serotonin Receptor Agonists, Thiazoles.
- drug effects : Brain, Neurons.
- drug therapy : Nerve Degeneration.
- pathology : Brain, Nerve Degeneration, Neurons.
- prevention & control : Parkinsonian Disorders.
- Animals, In Situ Hybridization, Macaca, Male, Mice, Mice, Inbred C57BL.
Abstract
Excitotoxicity-mediated cell death is involved in Parkinson's disease (PD). 5-HT1A receptor agonists can protect from such mechanisms. The current study demonstrates that the 5-HT1A agonists BAY 639044 and repinotan have neuroprotective effects in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In addition, we also show that both compounds delay the appearance of parkinsonian motor abnormalities in a MPTP monkey model that recapitulates the progressive nature of PD. Thus, BAY 639044 or repinotan treatment was initiated when there was 30% neuronal death in the substantia nigra pars compacta, and nerve terminal loss in the striatum was 40%, i.e., compatible with the clinical situation where early symptomatic patients would receive such a treatment. The delay in appearance of parkinsonian motor abnormalities is a consequence of partial neuroprotection of nigrostriatal dopamine neurons, both at neuronal and terminal levels as shown for BAY 639044. These results suggest that 5-HT1A agonists, such as BAY 639044, may protect from neurodegeneration and delay the worsening of motor symptoms in Parkinson patients.
DOI: 10.1016/j.nbd.2006.02.003
PubMed: 16545572
Affiliations:
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Gross</name></author><author><name sortKey="Jork, Reinhard" sort="Jork, Reinhard" uniqKey="Jork R" first="Reinhard" last="Jork">Reinhard Jork</name></author></analytic><series><title level="j">Neurobiology of disease</title><idno type="ISSN">0969-9961</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Benzopyrans (therapeutic use)</term><term>Brain (drug effects)</term><term>Brain (pathology)</term><term>In Situ Hybridization</term><term>Macaca</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Nerve Degeneration (drug therapy)</term><term>Nerve Degeneration (pathology)</term><term>Neurons (drug effects)</term><term>Neurons (pathology)</term><term>Neuroprotective Agents (therapeutic use)</term><term>Parkinsonian Disorders (prevention & control)</term><term>Receptor, Serotonin, 5-HT1A (drug effects)</term><term>Receptor, Serotonin, 5-HT1A (metabolism)</term><term>Serotonin Receptor Agonists (therapeutic use)</term><term>Thiazoles (therapeutic use)</term><term>Tyrosine 3-Monooxygenase (drug effects)</term><term>Tyrosine 3-Monooxygenase (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptor, Serotonin, 5-HT1A</term><term>Tyrosine 3-Monooxygenase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Receptor, Serotonin, 5-HT1A</term><term>Tyrosine 3-Monooxygenase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Benzopyrans</term><term>Neuroprotective Agents</term><term>Serotonin Receptor Agonists</term><term>Thiazoles</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Brain</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Nerve Degeneration</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term><term>Nerve Degeneration</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>In Situ Hybridization</term><term>Macaca</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Excitotoxicity-mediated cell death is involved in Parkinson's disease (PD). 5-HT1A receptor agonists can protect from such mechanisms. The current study demonstrates that the 5-HT1A agonists BAY 639044 and repinotan have neuroprotective effects in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In addition, we also show that both compounds delay the appearance of parkinsonian motor abnormalities in a MPTP monkey model that recapitulates the progressive nature of PD. Thus, BAY 639044 or repinotan treatment was initiated when there was 30% neuronal death in the substantia nigra pars compacta, and nerve terminal loss in the striatum was 40%, i.e., compatible with the clinical situation where early symptomatic patients would receive such a treatment. The delay in appearance of parkinsonian motor abnormalities is a consequence of partial neuroprotection of nigrostriatal dopamine neurons, both at neuronal and terminal levels as shown for BAY 639044. These results suggest that 5-HT1A agonists, such as BAY 639044, may protect from neurodegeneration and delay the worsening of motor symptoms in Parkinson patients.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16545572</PMID><DateCreated><Year>2006</Year><Month>06</Month><Day>21</Day></DateCreated><DateCompleted><Year>2006</Year><Month>09</Month><Day>06</Day></DateCompleted><DateRevised><Year>2010</Year><Month>11</Month><Day>18</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">0969-9961</ISSN><JournalIssue CitedMedium="Print"><Volume>23</Volume><Issue>1</Issue><PubDate><Year>2006</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Neurobiology of disease</Title><ISOAbbreviation>Neurobiol. Dis.</ISOAbbreviation></Journal><ArticleTitle>5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>77-86</MedlinePgn></Pagination><Abstract><AbstractText>Excitotoxicity-mediated cell death is involved in Parkinson's disease (PD). 5-HT1A receptor agonists can protect from such mechanisms. The current study demonstrates that the 5-HT1A agonists BAY 639044 and repinotan have neuroprotective effects in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In addition, we also show that both compounds delay the appearance of parkinsonian motor abnormalities in a MPTP monkey model that recapitulates the progressive nature of PD. Thus, BAY 639044 or repinotan treatment was initiated when there was 30% neuronal death in the substantia nigra pars compacta, and nerve terminal loss in the striatum was 40%, i.e., compatible with the clinical situation where early symptomatic patients would receive such a treatment. The delay in appearance of parkinsonian motor abnormalities is a consequence of partial neuroprotection of nigrostriatal dopamine neurons, both at neuronal and terminal levels as shown for BAY 639044. These results suggest that 5-HT1A agonists, such as BAY 639044, may protect from neurodegeneration and delay the worsening of motor symptoms in Parkinson patients.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bezard</LastName><ForeName>Erwan</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>CNRS UMR 5543, Laboratoire de Physiologie et Physiopathologie de la Signalisation Cellulaire, Université de Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux Cedex, France. erwan.bezard@umr5543.u-bordeaux2.fr</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gerlach</LastName><ForeName>Irene</ForeName><Initials>I</Initials></Author><Author ValidYN="Y"><LastName>Moratalla</LastName><ForeName>Rosario</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Gross</LastName><ForeName>Christian E</ForeName><Initials>CE</Initials></Author><Author ValidYN="Y"><LastName>Jork</LastName><ForeName>Reinhard</ForeName><Initials>R</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>2006</Year><Month>03</Month><Day>20</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Neurobiol Dis</MedlineTA><NlmUniqueID>9500169</NlmUniqueID><ISSNLinking>0969-9961</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C513036">BAY 639044</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001578">Benzopyrans</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018696">Neuroprotective 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MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009474" MajorTopicYN="N">Neurons</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018696" MajorTopicYN="N">Neuroprotective Agents</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020734" MajorTopicYN="N">Parkinsonian Disorders</DescriptorName><QualifierName UI="Q000517" MajorTopicYN="Y">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D044282" MajorTopicYN="N">Receptor, Serotonin, 5-HT1A</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017366" 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PubStatus="pubmed"><Year>2006</Year><Month>3</Month><Day>21</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2006</Year><Month>9</Month><Day>7</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>3</Month><Day>21</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">16545572</ArticleId><ArticleId IdType="pii">S0969-9961(06)00034-9</ArticleId><ArticleId IdType="doi">10.1016/j.nbd.2006.02.003</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>France</li></country><region><li>Aquitaine</li><li>Nouvelle-Aquitaine</li></region><settlement><li>Bordeaux</li></settlement></list><tree><noCountry><name sortKey="Gerlach, Irene" sort="Gerlach, Irene" uniqKey="Gerlach I" first="Irene" last="Gerlach">Irene Gerlach</name><name sortKey="Gross, Christian E" sort="Gross, Christian E" uniqKey="Gross C" first="Christian E" last="Gross">Christian E. Gross</name><name sortKey="Jork, Reinhard" sort="Jork, Reinhard" uniqKey="Jork R" first="Reinhard" last="Jork">Reinhard Jork</name><name sortKey="Moratalla, Rosario" sort="Moratalla, Rosario" uniqKey="Moratalla R" first="Rosario" last="Moratalla">Rosario Moratalla</name></noCountry><country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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