Neuronal protective and rescue effects of deprenyl against MPP+ dopaminergic toxicity
Identifieur interne : 000910 ( Main/Corpus ); précédent : 000909; suivant : 000911Neuronal protective and rescue effects of deprenyl against MPP+ dopaminergic toxicity
Auteurs : -M. Wu ; L. Murphy ; C. ChiuehSource :
- Journal of Neural Transmission / General Section JNT [ 0300-9564 ] ; 1995-02-01.
Abstract
Summary: Intranigral infusion of 1-Methyl-4-phenylpyridinium ion (MPP+, 2.1–16.8 nmol) dose-dependently injured nigral neurons as reflected by reduced dopamine levels in the ipsilateral striatum four days after the infusion of this toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Coadministration of deprenyl (4.2 nmol) with MPP+ into the substantia nigra protected against MPP+-induced moderate (20–50%) but not severe (over 70%) nigral injury as reflected in striatal dopamine reductions. However, supplementary treatment with deprenyl (0.25 mg/kg, s.c., twice daily for 4 days) after intranigral infusion of MPP+ significantly rescued nigral neurons from more severe damage caused by a higher MPP+ does (8.4 nmol) manifested by a lesser striatal dopamine decrease (−31%) compared to the non-deprenyl treated group (−70%). Thus, in addition to the blockade of bioactivation of MPTP, deprenyl can protect and/or rescue nigral neurons from MPP+-induced dopaminergic neurotoxicity. These in vivo data add further evidence to suggest that deprenyl, a putative and clinically unproven neuroprotective agent, may be of value in slowing the progressive nigral degeneration in “early” Parkinson's disease, but may prove to be less so in its terminal stages.
Url:
DOI: 10.1007/BF01276865
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Neuronal protective and rescue effects of deprenyl against MPP+ dopaminergic toxicity</title><author><name sortKey="Wu, M" sort="Wu, M" uniqKey="Wu " first="-M." last="Wu">-M. Wu</name><affiliation><mods:affiliation>Unit on Neurotoxicology and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan</mods:affiliation></affiliation></author><author><name sortKey="Murphy, L" sort="Murphy, L" uniqKey="Murphy L" first="L." last="Murphy">L. Murphy</name><affiliation><mods:affiliation>Section on Clinical Neuropharmacology, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</mods:affiliation></affiliation></author><author><name sortKey="Chiueh, C" sort="Chiueh, C" uniqKey="Chiueh C" first="C." last="Chiueh">C. Chiueh</name><affiliation><mods:affiliation>Unit on Neurotoxicology and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:86B5714BB8816374643E664DBAC8247692E9FAB3</idno><date when="1995" year="1995">1995</date><idno type="doi">10.1007/BF01276865</idno><idno type="url">https://api.istex.fr/document/86B5714BB8816374643E664DBAC8247692E9FAB3/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000910</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Neuronal protective and rescue effects of deprenyl against MPP+ dopaminergic toxicity</title><author><name sortKey="Wu, M" sort="Wu, M" uniqKey="Wu " first="-M." last="Wu">-M. Wu</name><affiliation><mods:affiliation>Unit on Neurotoxicology and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan</mods:affiliation></affiliation></author><author><name sortKey="Murphy, L" sort="Murphy, L" uniqKey="Murphy L" first="L." last="Murphy">L. Murphy</name><affiliation><mods:affiliation>Section on Clinical Neuropharmacology, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</mods:affiliation></affiliation></author><author><name sortKey="Chiueh, C" sort="Chiueh, C" uniqKey="Chiueh C" first="C." last="Chiueh">C. Chiueh</name><affiliation><mods:affiliation>Unit on Neurotoxicology and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Neural Transmission / General Section JNT</title><title level="j" type="abbrev">J. Neural Transmission</title><idno type="ISSN">0300-9564</idno><idno type="eISSN">1435-1463</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Vienna</pubPlace><date type="published" when="1995-02-01">1995-02-01</date><biblScope unit="volume">100</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="53">53</biblScope><biblScope unit="page" to="61">61</biblScope></imprint><idno type="ISSN">0300-9564</idno></series><idno type="istex">86B5714BB8816374643E664DBAC8247692E9FAB3</idno><idno type="DOI">10.1007/BF01276865</idno><idno type="ArticleID">Art6</idno><idno type="ArticleID">BF01276865</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0300-9564</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Summary: Intranigral infusion of 1-Methyl-4-phenylpyridinium ion (MPP+, 2.1–16.8 nmol) dose-dependently injured nigral neurons as reflected by reduced dopamine levels in the ipsilateral striatum four days after the infusion of this toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Coadministration of deprenyl (4.2 nmol) with MPP+ into the substantia nigra protected against MPP+-induced moderate (20–50%) but not severe (over 70%) nigral injury as reflected in striatal dopamine reductions. However, supplementary treatment with deprenyl (0.25 mg/kg, s.c., twice daily for 4 days) after intranigral infusion of MPP+ significantly rescued nigral neurons from more severe damage caused by a higher MPP+ does (8.4 nmol) manifested by a lesser striatal dopamine decrease (−31%) compared to the non-deprenyl treated group (−70%). Thus, in addition to the blockade of bioactivation of MPTP, deprenyl can protect and/or rescue nigral neurons from MPP+-induced dopaminergic neurotoxicity. These in vivo data add further evidence to suggest that deprenyl, a putative and clinically unproven neuroprotective agent, may be of value in slowing the progressive nigral degeneration in “early” Parkinson's disease, but may prove to be less so in its terminal stages.</div></front></TEI><istex><corpusName>springer</corpusName><author><json:item><name>R. -M. Wu</name><affiliations><json:string>Unit on Neurotoxicology and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</json:string><json:string>Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan</json:string></affiliations></json:item><json:item><name>D. L. Murphy</name><affiliations><json:string>Section on Clinical Neuropharmacology, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</json:string></affiliations></json:item><json:item><name>C. C. Chiueh</name><affiliations><json:string>Unit on Neurotoxicology and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</json:string></affiliations></json:item></author><articleId><json:string>Art6</json:string><json:string>BF01276865</json:string></articleId><language><json:string>eng</json:string></language><abstract>Summary: Intranigral infusion of 1-Methyl-4-phenylpyridinium ion (MPP+, 2.1–16.8 nmol) dose-dependently injured nigral neurons as reflected by reduced dopamine levels in the ipsilateral striatum four days after the infusion of this toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Coadministration of deprenyl (4.2 nmol) with MPP+ into the substantia nigra protected against MPP+-induced moderate (20–50%) but not severe (over 70%) nigral injury as reflected in striatal dopamine reductions. However, supplementary treatment with deprenyl (0.25 mg/kg, s.c., twice daily for 4 days) after intranigral infusion of MPP+ significantly rescued nigral neurons from more severe damage caused by a higher MPP+ does (8.4 nmol) manifested by a lesser striatal dopamine decrease (−31%) compared to the non-deprenyl treated group (−70%). Thus, in addition to the blockade of bioactivation of MPTP, deprenyl can protect and/or rescue nigral neurons from MPP+-induced dopaminergic neurotoxicity. These in vivo data add further evidence to suggest that deprenyl, a putative and clinically unproven neuroprotective agent, may be of value in slowing the progressive nigral degeneration in “early” Parkinson's disease, but may prove to be less so in its terminal stages.</abstract><qualityIndicators><score>6.35</score><pdfVersion>1.3</pdfVersion><pdfPageSize>576 x 774 pts</pdfPageSize><refBibsNative>false</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>1276</abstractCharCount><pdfWordCount>4226</pdfWordCount><pdfCharCount>24107</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>177</abstractWordCount></qualityIndicators><title>Neuronal protective and rescue effects of deprenyl against MPP+ dopaminergic toxicity</title><genre><json:string>research-article</json:string></genre><host><volume>100</volume><pages><last>61</last><first>53</first></pages><issn><json:string>0300-9564</json:string></issn><issue>1</issue><subject><json:item><value>Pharmacology/Toxicology</value></json:item><json:item><value>Neurology</value></json:item><json:item><value>Psychiatry</value></json:item></subject><journalId><json:string>702</json:string></journalId><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1435-1463</json:string></eissn><title>Journal of Neural Transmission / General Section JNT</title><publicationDate>1995</publicationDate><copyrightDate>1995</copyrightDate></host><publicationDate>1995</publicationDate><copyrightDate>1995</copyrightDate><doi><json:string>10.1007/BF01276865</json:string></doi><id>86B5714BB8816374643E664DBAC8247692E9FAB3</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/86B5714BB8816374643E664DBAC8247692E9FAB3/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/86B5714BB8816374643E664DBAC8247692E9FAB3/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/86B5714BB8816374643E664DBAC8247692E9FAB3/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Neuronal protective and rescue effects of deprenyl against MPP+ dopaminergic toxicity</title><respStmt xml:id="ISTEX-API" resp="Références bibliographiques récupérées via GROBID" name="ISTEX-API (INIST-CNRS)"></respStmt></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Springer-Verlag</publisher><pubPlace>Vienna</pubPlace><availability><p>SPRINGER</p></availability><date>1994-05-10</date></publicationStmt><notesStmt><note>Full Papers</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Neuronal protective and rescue effects of deprenyl against MPP+ dopaminergic toxicity</title><author><persName><forename type="first">R.</forename><surname>Wu</surname></persName><affiliation>Unit on Neurotoxicology and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</affiliation><affiliation>Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan</affiliation></author><author><persName><forename type="first">D.</forename><surname>Murphy</surname></persName><affiliation>Section on Clinical Neuropharmacology, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</affiliation></author><author><persName><forename type="first">C.</forename><surname>Chiueh</surname></persName><affiliation>Unit on Neurotoxicology and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</affiliation></author></analytic><monogr><title level="j">Journal of Neural Transmission / General Section JNT</title><title level="j" type="abbrev">J. Neural Transmission</title><idno type="JournalID">702</idno><idno type="pISSN">0300-9564</idno><idno type="eISSN">1435-1463</idno><idno type="IssueArticleCount">8</idno><idno type="VolumeIssueCount">3</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Vienna</pubPlace><date type="published" when="1995-02-01"></date><biblScope unit="volume">100</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="53">53</biblScope><biblScope unit="page" to="61">61</biblScope></imprint></monogr><idno type="istex">86B5714BB8816374643E664DBAC8247692E9FAB3</idno><idno type="DOI">10.1007/BF01276865</idno><idno type="ArticleID">Art6</idno><idno type="ArticleID">BF01276865</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1994-05-10</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Summary: Intranigral infusion of 1-Methyl-4-phenylpyridinium ion (MPP+, 2.1–16.8 nmol) dose-dependently injured nigral neurons as reflected by reduced dopamine levels in the ipsilateral striatum four days after the infusion of this toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Coadministration of deprenyl (4.2 nmol) with MPP+ into the substantia nigra protected against MPP+-induced moderate (20–50%) but not severe (over 70%) nigral injury as reflected in striatal dopamine reductions. However, supplementary treatment with deprenyl (0.25 mg/kg, s.c., twice daily for 4 days) after intranigral infusion of MPP+ significantly rescued nigral neurons from more severe damage caused by a higher MPP+ does (8.4 nmol) manifested by a lesser striatal dopamine decrease (−31%) compared to the non-deprenyl treated group (−70%). Thus, in addition to the blockade of bioactivation of MPTP, deprenyl can protect and/or rescue nigral neurons from MPP+-induced dopaminergic neurotoxicity. These in vivo data add further evidence to suggest that deprenyl, a putative and clinically unproven neuroprotective agent, may be of value in slowing the progressive nigral degeneration in “early” Parkinson's disease, but may prove to be less so in its terminal stages.</p></abstract><textClass><keywords scheme="Journal Subject"><list><head>Medicine & Public Health</head><item><term>Pharmacology/Toxicology</term></item><item><term>Neurology</term></item><item><term>Psychiatry</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1994-05-10">Created</change><change when="1995-02-01">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-3-1">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/86B5714BB8816374643E664DBAC8247692E9FAB3/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Springer, Publisher found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//Springer-Verlag//DTD A++ V2.4//EN" URI="http://devel.springer.de/A++/V2.4/DTD/A++V2.4.dtd" name="istex:docType"></istex:docType><istex:document><Publisher><PublisherInfo><PublisherName>Springer-Verlag</PublisherName><PublisherLocation>Vienna</PublisherLocation></PublisherInfo><Journal><JournalInfo JournalProductType="ArchiveJournal" NumberingStyle="Unnumbered"><JournalID>702</JournalID><JournalPrintISSN>0300-9564</JournalPrintISSN><JournalElectronicISSN>1435-1463</JournalElectronicISSN><JournalTitle>Journal of Neural Transmission / General Section JNT</JournalTitle><JournalAbbreviatedTitle>J. 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Coadministration of deprenyl (4.2 nmol) with MPP<Superscript>+</Superscript> into the substantia nigra protected against MPP<Superscript>+</Superscript>-induced moderate (20–50%) but not severe (over 70%) nigral injury as reflected in striatal dopamine reductions. However, supplementary treatment with deprenyl (0.25 mg/kg, s.c., twice daily for 4 days) after intranigral infusion of MPP<Superscript>+</Superscript> significantly rescued nigral neurons from more severe damage caused by a higher MPP<Superscript>+</Superscript> does (8.4 nmol) manifested by a lesser striatal dopamine decrease (−31%) compared to the non-deprenyl treated group (−70%). Thus, in addition to the blockade of bioactivation of MPTP, deprenyl can protect and/or rescue nigral neurons from MPP<Superscript>+</Superscript>-induced dopaminergic neurotoxicity. These in vivo data add further evidence to suggest that deprenyl, a putative and clinically unproven neuroprotective agent, may be of value in slowing the progressive nigral degeneration in “early” Parkinson's disease, but may prove to be less so in its terminal stages.</Para></Abstract><KeywordGroup Language="En"><Heading>Keywords</Heading><Keyword>Deprenyl (selegiline)</Keyword><Keyword>MPTP</Keyword><Keyword>MPP<Superscript>+</Superscript></Keyword><Keyword>Parkinson's disease</Keyword><Keyword>dopamine</Keyword><Keyword>substantia nigra</Keyword><Keyword>nigrostriatal neuron</Keyword></KeywordGroup></ArticleHeader><NoBody></NoBody></Article></Issue></Volume></Journal></Publisher></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Neuronal protective and rescue effects of deprenyl against MPP+ dopaminergic toxicity</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Neuronal protective and rescue effects of deprenyl against MPP+ dopaminergic toxicity</title></titleInfo><name type="personal"><namePart type="given">R.</namePart><namePart type="given">-M.</namePart><namePart type="family">Wu</namePart><affiliation>Unit on Neurotoxicology and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</affiliation><affiliation>Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D.</namePart><namePart type="given">L.</namePart><namePart type="family">Murphy</namePart><affiliation>Section on Clinical Neuropharmacology, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="given">C.</namePart><namePart type="family">Chiueh</namePart><affiliation>Unit on Neurotoxicology and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center 10/3D-41, Bethesda, Maryland, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="OriginalPaper"></genre><originInfo><publisher>Springer-Verlag</publisher><place><placeTerm type="text">Vienna</placeTerm></place><dateCreated encoding="w3cdtf">1994-05-10</dateCreated><dateIssued encoding="w3cdtf">1995-02-01</dateIssued><copyrightDate encoding="w3cdtf">1995</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Summary: Intranigral infusion of 1-Methyl-4-phenylpyridinium ion (MPP+, 2.1–16.8 nmol) dose-dependently injured nigral neurons as reflected by reduced dopamine levels in the ipsilateral striatum four days after the infusion of this toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Coadministration of deprenyl (4.2 nmol) with MPP+ into the substantia nigra protected against MPP+-induced moderate (20–50%) but not severe (over 70%) nigral injury as reflected in striatal dopamine reductions. However, supplementary treatment with deprenyl (0.25 mg/kg, s.c., twice daily for 4 days) after intranigral infusion of MPP+ significantly rescued nigral neurons from more severe damage caused by a higher MPP+ does (8.4 nmol) manifested by a lesser striatal dopamine decrease (−31%) compared to the non-deprenyl treated group (−70%). Thus, in addition to the blockade of bioactivation of MPTP, deprenyl can protect and/or rescue nigral neurons from MPP+-induced dopaminergic neurotoxicity. These in vivo data add further evidence to suggest that deprenyl, a putative and clinically unproven neuroprotective agent, may be of value in slowing the progressive nigral degeneration in “early” Parkinson's disease, but may prove to be less so in its terminal stages.</abstract><note>Full Papers</note><relatedItem type="host"><titleInfo><title>Journal of Neural Transmission / General Section JNT</title></titleInfo><titleInfo type="abbreviated"><title>J. Neural Transmission</title></titleInfo><genre type="Journal" displayLabel="Archive Journal"></genre><originInfo><dateIssued encoding="w3cdtf">1995-02-01</dateIssued><copyrightDate encoding="w3cdtf">1995</copyrightDate></originInfo><subject><genre>Medicine & Public Health</genre><topic>Pharmacology/Toxicology</topic><topic>Neurology</topic><topic>Psychiatry</topic></subject><identifier type="ISSN">0300-9564</identifier><identifier type="eISSN">1435-1463</identifier><identifier type="JournalID">702</identifier><identifier type="IssueArticleCount">8</identifier><identifier type="VolumeIssueCount">3</identifier><part><date>1995</date><detail type="volume"><number>100</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="pages"><start>53</start><end>61</end></extent></part><recordInfo><recordOrigin>Springer-Verlag, 1995</recordOrigin></recordInfo></relatedItem><identifier 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