Unexpected toxicity of very low dose MPTP in mice: A clue to the etiology of Parkinson's disease?
Identifieur interne : 000200 ( PubMed/Corpus ); précédent : 000199; suivant : 000201Unexpected toxicity of very low dose MPTP in mice: A clue to the etiology of Parkinson's disease?
Auteurs : Sandra Dovero ; Christian Gross ; Erwan BezardSource :
- Synapse (New York, N.Y.) [ 1098-2396 ] ; 2016.
English descriptors
- KwdEn :
- MESH :
- chemical , administration & dosage : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- chemical , pharmacology : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- drug effects : Dopaminergic Neurons.
- etiology : Parkinson Disease.
- metabolism : MPTP Poisoning.
- Animals, Dose-Response Relationship, Drug, Mice.
Abstract
Although much progress have been made in recent years, the etiology of idiopathic Parkinson's disease remains obscure. The chance discovery that injection of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces a syndrome very similar to parkinsonism introduced the "environmental toxin" hypothesis but no toxin was ever found in any quantity in patients' brains. We have unexpectedly now found, however, that, in mice, very low doses of MPTP induce as much dopaminergic neuronal death as far higher doses. Cellular detoxification mechanisms would appear to be incapacitated at such low doses. This could infer that the barely discernible presence of an unidentified neurotoxin may be responsible for the onset of Parkinson's disease.
DOI: 10.1002/syn.21875
PubMed: 26583879
Links to Exploration step
pubmed:26583879Le document en format XML
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De Bordeaux, Institut Des Maladies Neurodégénératives, Bordeaux, France.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26583879</idno><idno type="pmid">26583879</idno><idno type="doi">10.1002/syn.21875</idno><idno type="wicri:Area/PubMed/Corpus">000200</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000200</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Unexpected toxicity of very low dose MPTP in mice: A clue to the etiology of Parkinson's disease?</title><author><name sortKey="Dovero, Sandra" sort="Dovero, Sandra" uniqKey="Dovero S" first="Sandra" last="Dovero">Sandra Dovero</name><affiliation><nlm:affiliation>Univ. De Bordeaux, Institut Des Maladies Neurodégénératives, Bordeaux, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gross, Christian" sort="Gross, Christian" uniqKey="Gross C" first="Christian" last="Gross">Christian Gross</name><affiliation><nlm:affiliation>Univ. De Bordeaux, Institut Des Maladies Neurodégénératives, Bordeaux, France.</nlm:affiliation></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation><nlm:affiliation>Univ. De Bordeaux, Institut Des Maladies Neurodégénératives, Bordeaux, France.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Synapse (New York, N.Y.)</title><idno type="eISSN">1098-2396</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (administration & dosage)</term><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology)</term><term>Animals</term><term>Dopaminergic Neurons (drug effects)</term><term>Dose-Response Relationship, Drug</term><term>MPTP Poisoning (metabolism)</term><term>Mice</term><term>Parkinson Disease (etiology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Dopaminergic Neurons</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>MPTP Poisoning</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Dose-Response Relationship, Drug</term><term>Mice</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Although much progress have been made in recent years, the etiology of idiopathic Parkinson's disease remains obscure. The chance discovery that injection of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces a syndrome very similar to parkinsonism introduced the "environmental toxin" hypothesis but no toxin was ever found in any quantity in patients' brains. We have unexpectedly now found, however, that, in mice, very low doses of MPTP induce as much dopaminergic neuronal death as far higher doses. Cellular detoxification mechanisms would appear to be incapacitated at such low doses. This could infer that the barely discernible presence of an unidentified neurotoxin may be responsible for the onset of Parkinson's disease.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26583879</PMID><DateCreated><Year>2016</Year><Month>01</Month><Day>15</Day></DateCreated><DateCompleted><Year>2016</Year><Month>10</Month><Day>05</Day></DateCompleted><DateRevised><Year>2016</Year><Month>12</Month><Day>30</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1098-2396</ISSN><JournalIssue CitedMedium="Internet"><Volume>70</Volume><Issue>2</Issue><PubDate><Year>2016</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Synapse (New York, N.Y.)</Title><ISOAbbreviation>Synapse</ISOAbbreviation></Journal><ArticleTitle>Unexpected toxicity of very low dose MPTP in mice: A clue to the etiology of Parkinson's disease?</ArticleTitle><Pagination><MedlinePgn>49-51</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/syn.21875</ELocationID><Abstract><AbstractText>Although much progress have been made in recent years, the etiology of idiopathic Parkinson's disease remains obscure. The chance discovery that injection of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces a syndrome very similar to parkinsonism introduced the "environmental toxin" hypothesis but no toxin was ever found in any quantity in patients' brains. We have unexpectedly now found, however, that, in mice, very low doses of MPTP induce as much dopaminergic neuronal death as far higher doses. Cellular detoxification mechanisms would appear to be incapacitated at such low doses. This could infer that the barely discernible presence of an unidentified neurotoxin may be responsible for the onset of Parkinson's disease.</AbstractText><CopyrightInformation>© 2015 Wiley Periodicals, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Dovero</LastName><ForeName>Sandra</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Univ. De Bordeaux, Institut Des Maladies Neurodégénératives, Bordeaux, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institut Des Maladies Neurodégénératives, CNRS, Bordeaux, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gross</LastName><ForeName>Christian</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Univ. De Bordeaux, Institut Des Maladies Neurodégénératives, Bordeaux, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institut Des Maladies Neurodégénératives, CNRS, Bordeaux, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bezard</LastName><ForeName>Erwan</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Univ. De Bordeaux, Institut Des Maladies Neurodégénératives, Bordeaux, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institut Des Maladies Neurodégénératives, CNRS, Bordeaux, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>12</Month><Day>01</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Synapse</MedlineTA><NlmUniqueID>8806914</NlmUniqueID><ISSNLinking>0887-4476</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>9P21XSP91P</RegistryNumber><NameOfSubstance UI="D015632">1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D015632" MajorTopicYN="N">1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059290" MajorTopicYN="N">Dopaminergic Neurons</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020267" MajorTopicYN="N">MPTP Poisoning</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">MPTP</Keyword><Keyword MajorTopicYN="N">Parkinson's disease</Keyword><Keyword MajorTopicYN="N">aetiology</Keyword><Keyword MajorTopicYN="N">cellular detoxification</Keyword><Keyword MajorTopicYN="N">mouse</Keyword><Keyword MajorTopicYN="N">toxin hypothesis</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>10</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>11</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>11</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>11</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>10</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26583879</ArticleId><ArticleId IdType="doi">10.1002/syn.21875</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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