Catechols in post‐mortem brain of patients with Parkinson disease
Identifieur interne : 000001 ( Main/Corpus ); précédent : 000000; suivant : 000002Catechols in post‐mortem brain of patients with Parkinson disease
Auteurs : D. S. Goldstein ; P. Sullivan ; C. Holmes ; I. J. Kopin ; M. J. Basile ; D. C. MashSource :
- European Journal of Neurology [ 1351-5101 ] ; 2011-05.
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- KwdEn :
Abstract
Background: Dihydroxyphenylacetaldehyde (DOPAL), a cytotoxic metabolite of dopamine, is the focus of the ‘catecholaldehyde hypothesis’ about the pathogenesis of Parkinson disease. This study explored whether DOPAL is detectable in human striatum – especially in the putamen (Pu), the main site of dopamine depletion in Parkinson disease – and is related to other neurochemical indices of catecholamine stores and metabolism in Parkinson disease. Methods: Putamen, caudate (Cd), and frontal cortex (Ctx) catechols were measured in tissue from patients with pathologically proven end‐stage Parkinson disease (N = 15) and control subjects (N = 14) of similar age with similar post‐mortem intervals. Results: Putamen DOPAL (3% of dopamine in controls) correlated with dopamine and dihydroxyphenylacetic acid both across all subjects and within the Parkinson disease and control groups. Pu dopamine was decreased by 93% and dihydroxyphenylacetic acid 95% in Parkinson disease vs. controls, with smaller decreases of DOPAL (83%) and norepinephrine (73%) in Pu and of dopamine (74%) and dihydroxyphenylacetic acid (82%) in Cd. In Parkinson disease, Pu DOPAL:dihydroxyphenylacetic acid averaged 3.4 times and DOPAL:dopamine 4.4 times control (P = 0.03 each). The main catecholamine in Ctx was norepinephrine, which was decreased by 51% in Parkinson disease patients. Conclusions: Correlated decreases of DOPAL, dopamine, and dihydroxyphenylacetic acid in Parkinson disease reflect severe loss of Pu dopamine stores, which seems more extensive than loss of Pu norepinephrine or Cd dopamine stores. Increased Pu DOPAL:dihydroxyphenylacetic acid ratios in Parkinson disease suggest decreased detoxification of DOPAL by aldehyde dehydrogenase. Elevated levels of cytosolic DOPAL might contribute to loss of dopaminergic neurons in Parkinson disease.
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DOI: 10.1111/j.1468-1331.2010.03246.x
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Catechols in post‐mortem brain of patients with Parkinson disease</title><author><name sortKey="Goldstein, D S" sort="Goldstein, D S" uniqKey="Goldstein D" first="D. S." last="Goldstein">D. S. Goldstein</name><affiliation><mods:affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</mods:affiliation></affiliation></author><author><name sortKey="Sullivan, P" sort="Sullivan, P" uniqKey="Sullivan P" first="P." last="Sullivan">P. Sullivan</name><affiliation><mods:affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</mods:affiliation></affiliation></author><author><name sortKey="Holmes, C" sort="Holmes, C" uniqKey="Holmes C" first="C." last="Holmes">C. Holmes</name><affiliation><mods:affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</mods:affiliation></affiliation></author><author><name sortKey="Kopin, I J" sort="Kopin, I J" uniqKey="Kopin I" first="I. J." last="Kopin">I. J. Kopin</name><affiliation><mods:affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</mods:affiliation></affiliation></author><author><name sortKey="Basile, M J" sort="Basile, M J" uniqKey="Basile M" first="M. J." last="Basile">M. J. Basile</name><affiliation><mods:affiliation>Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA</mods:affiliation></affiliation></author><author><name sortKey="Mash, D C" sort="Mash, D C" uniqKey="Mash D" first="D. C." last="Mash">D. C. 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Goldstein</name><affiliation><mods:affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</mods:affiliation></affiliation></author><author><name sortKey="Sullivan, P" sort="Sullivan, P" uniqKey="Sullivan P" first="P." last="Sullivan">P. Sullivan</name><affiliation><mods:affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</mods:affiliation></affiliation></author><author><name sortKey="Holmes, C" sort="Holmes, C" uniqKey="Holmes C" first="C." last="Holmes">C. Holmes</name><affiliation><mods:affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</mods:affiliation></affiliation></author><author><name sortKey="Kopin, I J" sort="Kopin, I J" uniqKey="Kopin I" first="I. J." last="Kopin">I. J. Kopin</name><affiliation><mods:affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</mods:affiliation></affiliation></author><author><name sortKey="Basile, M J" sort="Basile, M J" uniqKey="Basile M" first="M. J." last="Basile">M. J. Basile</name><affiliation><mods:affiliation>Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA</mods:affiliation></affiliation></author><author><name sortKey="Mash, D C" sort="Mash, D C" uniqKey="Mash D" first="D. C." last="Mash">D. C. Mash</name><affiliation><mods:affiliation>Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">European Journal of Neurology</title><idno type="ISSN">1351-5101</idno><idno type="eISSN">1468-1331</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2011-05">2011-05</date><biblScope unit="volume">18</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="703">703</biblScope><biblScope unit="page" to="710">710</biblScope></imprint><idno type="ISSN">1351-5101</idno></series><idno type="istex">A8053DC4D0F138A958805F51B310A5D9348C2811</idno><idno type="DOI">10.1111/j.1468-1331.2010.03246.x</idno><idno type="ArticleID">ENE3246</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1351-5101</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson disease</term><term>aldehyde dehydrogenase</term><term>dihydroxyphenylacetaldehyde</term><term>dihydroxyphenylglycol</term><term>dopamine</term><term>norepinephrine</term><term>putamen</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: Dihydroxyphenylacetaldehyde (DOPAL), a cytotoxic metabolite of dopamine, is the focus of the ‘catecholaldehyde hypothesis’ about the pathogenesis of Parkinson disease. This study explored whether DOPAL is detectable in human striatum – especially in the putamen (Pu), the main site of dopamine depletion in Parkinson disease – and is related to other neurochemical indices of catecholamine stores and metabolism in Parkinson disease. Methods: Putamen, caudate (Cd), and frontal cortex (Ctx) catechols were measured in tissue from patients with pathologically proven end‐stage Parkinson disease (N = 15) and control subjects (N = 14) of similar age with similar post‐mortem intervals. Results: Putamen DOPAL (3% of dopamine in controls) correlated with dopamine and dihydroxyphenylacetic acid both across all subjects and within the Parkinson disease and control groups. Pu dopamine was decreased by 93% and dihydroxyphenylacetic acid 95% in Parkinson disease vs. controls, with smaller decreases of DOPAL (83%) and norepinephrine (73%) in Pu and of dopamine (74%) and dihydroxyphenylacetic acid (82%) in Cd. In Parkinson disease, Pu DOPAL:dihydroxyphenylacetic acid averaged 3.4 times and DOPAL:dopamine 4.4 times control (P = 0.03 each). The main catecholamine in Ctx was norepinephrine, which was decreased by 51% in Parkinson disease patients. Conclusions: Correlated decreases of DOPAL, dopamine, and dihydroxyphenylacetic acid in Parkinson disease reflect severe loss of Pu dopamine stores, which seems more extensive than loss of Pu norepinephrine or Cd dopamine stores. Increased Pu DOPAL:dihydroxyphenylacetic acid ratios in Parkinson disease suggest decreased detoxification of DOPAL by aldehyde dehydrogenase. Elevated levels of cytosolic DOPAL might contribute to loss of dopaminergic neurons in Parkinson disease.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>D. S. Goldstein</name><affiliations><json:string>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</json:string></affiliations></json:item><json:item><name>P. Sullivan</name><affiliations><json:string>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</json:string></affiliations></json:item><json:item><name>C. Holmes</name><affiliations><json:string>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</json:string></affiliations></json:item><json:item><name>I. J. Kopin</name><affiliations><json:string>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</json:string></affiliations></json:item><json:item><name>M. J. Basile</name><affiliations><json:string>Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA</json:string></affiliations></json:item><json:item><name>D. C. Mash</name><affiliations><json:string>Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>aldehyde dehydrogenase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dihydroxyphenylacetaldehyde</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dihydroxyphenylglycol</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dopamine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>norepinephrine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>putamen</value></json:item></subject><articleId><json:string>ENE3246</json:string></articleId><language><json:string>eng</json:string></language><abstract>Background: Dihydroxyphenylacetaldehyde (DOPAL), a cytotoxic metabolite of dopamine, is the focus of the ‘catecholaldehyde hypothesis’ about the pathogenesis of Parkinson disease. This study explored whether DOPAL is detectable in human striatum – especially in the putamen (Pu), the main site of dopamine depletion in Parkinson disease – and is related to other neurochemical indices of catecholamine stores and metabolism in Parkinson disease. Methods: Putamen, caudate (Cd), and frontal cortex (Ctx) catechols were measured in tissue from patients with pathologically proven end‐stage Parkinson disease (N = 15) and control subjects (N = 14) of similar age with similar post‐mortem intervals. Results: Putamen DOPAL (3% of dopamine in controls) correlated with dopamine and dihydroxyphenylacetic acid both across all subjects and within the Parkinson disease and control groups. Pu dopamine was decreased by 93% and dihydroxyphenylacetic acid 95% in Parkinson disease vs. controls, with smaller decreases of DOPAL (83%) and norepinephrine (73%) in Pu and of dopamine (74%) and dihydroxyphenylacetic acid (82%) in Cd. In Parkinson disease, Pu DOPAL:dihydroxyphenylacetic acid averaged 3.4 times and DOPAL:dopamine 4.4 times control (P = 0.03 each). The main catecholamine in Ctx was norepinephrine, which was decreased by 51% in Parkinson disease patients. Conclusions: Correlated decreases of DOPAL, dopamine, and dihydroxyphenylacetic acid in Parkinson disease reflect severe loss of Pu dopamine stores, which seems more extensive than loss of Pu norepinephrine or Cd dopamine stores. Increased Pu DOPAL:dihydroxyphenylacetic acid ratios in Parkinson disease suggest decreased detoxification of DOPAL by aldehyde dehydrogenase. Elevated levels of cytosolic DOPAL might contribute to loss of dopaminergic neurons in Parkinson disease.</abstract><qualityIndicators><score>6.636</score><pdfVersion>1.3</pdfVersion><pdfPageSize>595.276 x 782.362 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>7</keywordCount><abstractCharCount>1841</abstractCharCount><pdfWordCount>3636</pdfWordCount><pdfCharCount>26754</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>252</abstractWordCount></qualityIndicators><title>Catechols in post‐mortem brain of patients with Parkinson disease</title><genre><json:string>article</json:string></genre><host><volume>18</volume><publisherId><json:string>ENE</json:string></publisherId><pages><total>8</total><last>710</last><first>703</first></pages><issn><json:string>1351-5101</json:string></issn><issue>5</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1468-1331</json:string></eissn><title>European Journal of Neurology</title><doi><json:string>10.1111/(ISSN)1468-1331</json:string></doi></host><publicationDate>2011</publicationDate><copyrightDate>2011</copyrightDate><doi><json:string>10.1111/j.1468-1331.2010.03246.x</json:string></doi><id>A8053DC4D0F138A958805F51B310A5D9348C2811</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/A8053DC4D0F138A958805F51B310A5D9348C2811/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/A8053DC4D0F138A958805F51B310A5D9348C2811/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/A8053DC4D0F138A958805F51B310A5D9348C2811/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Catechols in post‐mortem brain of patients with Parkinson disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><availability><p>WILEY</p></availability><date>2011</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Catechols in post‐mortem brain of patients with Parkinson disease</title><author><persName><forename type="first">D. S.</forename><surname>Goldstein</surname></persName><affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</affiliation></author><author><persName><forename type="first">P.</forename><surname>Sullivan</surname></persName><affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</affiliation></author><author><persName><forename type="first">C.</forename><surname>Holmes</surname></persName><affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</affiliation></author><author><persName><forename type="first">I. J.</forename><surname>Kopin</surname></persName><affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</affiliation></author><author><persName><forename type="first">M. J.</forename><surname>Basile</surname></persName><affiliation>Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA</affiliation></author><author><persName><forename type="first">D. C.</forename><surname>Mash</surname></persName><affiliation>Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA</affiliation></author></analytic><monogr><title level="j">European Journal of Neurology</title><idno type="pISSN">1351-5101</idno><idno type="eISSN">1468-1331</idno><idno type="DOI">10.1111/(ISSN)1468-1331</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2011-05"></date><biblScope unit="volume">18</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="703">703</biblScope><biblScope unit="page" to="710">710</biblScope></imprint></monogr><idno type="istex">A8053DC4D0F138A958805F51B310A5D9348C2811</idno><idno type="DOI">10.1111/j.1468-1331.2010.03246.x</idno><idno type="ArticleID">ENE3246</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Background: Dihydroxyphenylacetaldehyde (DOPAL), a cytotoxic metabolite of dopamine, is the focus of the ‘catecholaldehyde hypothesis’ about the pathogenesis of Parkinson disease. This study explored whether DOPAL is detectable in human striatum – especially in the putamen (Pu), the main site of dopamine depletion in Parkinson disease – and is related to other neurochemical indices of catecholamine stores and metabolism in Parkinson disease. Methods: Putamen, caudate (Cd), and frontal cortex (Ctx) catechols were measured in tissue from patients with pathologically proven end‐stage Parkinson disease (N = 15) and control subjects (N = 14) of similar age with similar post‐mortem intervals. Results: Putamen DOPAL (3% of dopamine in controls) correlated with dopamine and dihydroxyphenylacetic acid both across all subjects and within the Parkinson disease and control groups. Pu dopamine was decreased by 93% and dihydroxyphenylacetic acid 95% in Parkinson disease vs. controls, with smaller decreases of DOPAL (83%) and norepinephrine (73%) in Pu and of dopamine (74%) and dihydroxyphenylacetic acid (82%) in Cd. In Parkinson disease, Pu DOPAL:dihydroxyphenylacetic acid averaged 3.4 times and DOPAL:dopamine 4.4 times control (P = 0.03 each). The main catecholamine in Ctx was norepinephrine, which was decreased by 51% in Parkinson disease patients. Conclusions: Correlated decreases of DOPAL, dopamine, and dihydroxyphenylacetic acid in Parkinson disease reflect severe loss of Pu dopamine stores, which seems more extensive than loss of Pu norepinephrine or Cd dopamine stores. Increased Pu DOPAL:dihydroxyphenylacetic acid ratios in Parkinson disease suggest decreased detoxification of DOPAL by aldehyde dehydrogenase. Elevated levels of cytosolic DOPAL might contribute to loss of dopaminergic neurons in Parkinson disease.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>aldehyde dehydrogenase</term></item><item><term>dihydroxyphenylacetaldehyde</term></item><item><term>dihydroxyphenylglycol</term></item><item><term>dopamine</term></item><item><term>norepinephrine</term></item><item><term>Parkinson disease</term></item><item><term>putamen</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2011-05">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/A8053DC4D0F138A958805F51B310A5D9348C2811/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Publishing Ltd</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1468-1331</doi><issn type="print">1351-5101</issn><issn type="electronic">1468-1331</issn><idGroup><id type="product" value="ENE"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="EUROPEAN JOURNAL OF NEUROLOGY">European Journal of Neurology</title></titleGroup></publicationMeta><publicationMeta level="part" position="05105"><doi origin="wiley">10.1111/ene.2011.18.issue-5</doi><numberingGroup><numbering type="journalVolume" number="18">18</numbering><numbering type="journalIssue" number="5">5</numbering></numberingGroup><coverDate startDate="2011-05">May 2011</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="6" status="forIssue"><doi origin="wiley">10.1111/j.1468-1331.2010.03246.x</doi><idGroup><id type="unit" value="ENE3246"></id></idGroup><countGroup><count type="pageTotal" number="8"></count></countGroup><titleGroup><title type="tocHeading1">Original Articles</title></titleGroup><copyright>No claim to original US government works. European Journal of Neurology © 2010 EFNS</copyright><eventGroup><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.4.8 mode:FullText" date="2011-04-14"></event><event type="publishedOnlineEarlyUnpaginated" date="2010-11-12"></event><event type="firstOnline" date="2010-11-12"></event><event type="publishedOnlineFinalForm" date="2011-04-15"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-24"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-16"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="703">703</numbering><numbering type="pageLast" number="710">710</numbering></numberingGroup><correspondenceTo>David S. Goldstein, Clinical Neurocardiology Section, NINDS, NIH, 9000 Rockville Pike MSC‐1620, Building 10 Room 5N220, Bethesda, MD 20892‐1620, USA (tel.: 301 496 2103; fax: 301 402 0180; e‐mail: <email>goldsteind@ninds.nih.gov</email>).</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:ENE.ENE3246.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received 29 June 2010 Accepted 13 September 2010</unparsedEditorialHistory><countGroup><count type="figureTotal" number="5"></count><count type="tableTotal" number="3"></count></countGroup><titleGroup><title type="main">Catechols in post‐mortem brain of patients with Parkinson disease</title><title type="shortAuthors">D. S. Goldstein <i>et al.</i></title><title type="short">Brain catechols in Parkinson disease</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>D. S.</givenNames><familyName>Goldstein</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>P.</givenNames><familyName>Sullivan</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1"><personName><givenNames>C.</givenNames><familyName>Holmes</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a1"><personName><givenNames>I. J.</givenNames><familyName>Kopin</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a2"><personName><givenNames>M. J.</givenNames><familyName>Basile</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a2"><personName><givenNames>D. C.</givenNames><familyName>Mash</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1"><unparsedAffiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="US"><unparsedAffiliation>Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">aldehyde dehydrogenase</keyword><keyword xml:id="k2">dihydroxyphenylacetaldehyde</keyword><keyword xml:id="k3">dihydroxyphenylglycol</keyword><keyword xml:id="k4">dopamine</keyword><keyword xml:id="k5">norepinephrine</keyword><keyword xml:id="k6">Parkinson disease</keyword><keyword xml:id="k7">putamen</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p><b>Background: </b> Dihydroxyphenylacetaldehyde (DOPAL), a cytotoxic metabolite of dopamine, is the focus of the ‘catecholaldehyde hypothesis’ about the pathogenesis of Parkinson disease. This study explored whether DOPAL is detectable in human striatum – especially in the putamen (Pu), the main site of dopamine depletion in Parkinson disease – and is related to other neurochemical indices of catecholamine stores and metabolism in Parkinson disease.</p><p><b>Methods: </b> Putamen, caudate (Cd), and frontal cortex (Ctx) catechols were measured in tissue from patients with pathologically proven end‐stage Parkinson disease (<i>N </i>= 15) and control subjects (<i>N </i>= 14) of similar age with similar post‐mortem intervals.</p><p><b>Results: </b> Putamen DOPAL (3% of dopamine in controls) correlated with dopamine and dihydroxyphenylacetic acid both across all subjects and within the Parkinson disease and control groups. Pu dopamine was decreased by 93% and dihydroxyphenylacetic acid 95% in Parkinson disease vs. controls, with smaller decreases of DOPAL (83%) and norepinephrine (73%) in Pu and of dopamine (74%) and dihydroxyphenylacetic acid (82%) in Cd. In Parkinson disease, Pu DOPAL:dihydroxyphenylacetic acid averaged 3.4 times and DOPAL:dopamine 4.4 times control (<i>P </i>= 0.03 each). The main catecholamine in Ctx was norepinephrine, which was decreased by 51% in Parkinson disease patients.</p><p><b>Conclusions: </b> Correlated decreases of DOPAL, dopamine, and dihydroxyphenylacetic acid in Parkinson disease reflect severe loss of Pu dopamine stores, which seems more extensive than loss of Pu norepinephrine or Cd dopamine stores. Increased Pu DOPAL:dihydroxyphenylacetic acid ratios in Parkinson disease suggest decreased detoxification of DOPAL by aldehyde dehydrogenase. Elevated levels of cytosolic DOPAL might contribute to loss of dopaminergic neurons in Parkinson disease.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Catechols in post‐mortem brain of patients with Parkinson disease</title></titleInfo><titleInfo type="abbreviated"><title>Brain catechols in Parkinson disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Catechols in post‐mortem brain of patients with Parkinson disease</title></titleInfo><name type="personal"><namePart type="given">D. S.</namePart><namePart type="family">Goldstein</namePart><affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P.</namePart><namePart type="family">Sullivan</namePart><affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="family">Holmes</namePart><affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">I. J.</namePart><namePart type="family">Kopin</namePart><affiliation>Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M. J.</namePart><namePart type="family">Basile</namePart><affiliation>Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D. C.</namePart><namePart type="family">Mash</namePart><affiliation>Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2011-05</dateIssued><edition>Received 29 June 2010 Accepted 13 September 2010</edition><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">5</extent><extent unit="tables">3</extent></physicalDescription><abstract lang="en">Background: Dihydroxyphenylacetaldehyde (DOPAL), a cytotoxic metabolite of dopamine, is the focus of the ‘catecholaldehyde hypothesis’ about the pathogenesis of Parkinson disease. This study explored whether DOPAL is detectable in human striatum – especially in the putamen (Pu), the main site of dopamine depletion in Parkinson disease – and is related to other neurochemical indices of catecholamine stores and metabolism in Parkinson disease. Methods: Putamen, caudate (Cd), and frontal cortex (Ctx) catechols were measured in tissue from patients with pathologically proven end‐stage Parkinson disease (N = 15) and control subjects (N = 14) of similar age with similar post‐mortem intervals. Results: Putamen DOPAL (3% of dopamine in controls) correlated with dopamine and dihydroxyphenylacetic acid both across all subjects and within the Parkinson disease and control groups. Pu dopamine was decreased by 93% and dihydroxyphenylacetic acid 95% in Parkinson disease vs. controls, with smaller decreases of DOPAL (83%) and norepinephrine (73%) in Pu and of dopamine (74%) and dihydroxyphenylacetic acid (82%) in Cd. In Parkinson disease, Pu DOPAL:dihydroxyphenylacetic acid averaged 3.4 times and DOPAL:dopamine 4.4 times control (P = 0.03 each). The main catecholamine in Ctx was norepinephrine, which was decreased by 51% in Parkinson disease patients. Conclusions: Correlated decreases of DOPAL, dopamine, and dihydroxyphenylacetic acid in Parkinson disease reflect severe loss of Pu dopamine stores, which seems more extensive than loss of Pu norepinephrine or Cd dopamine stores. Increased Pu DOPAL:dihydroxyphenylacetic acid ratios in Parkinson disease suggest decreased detoxification of DOPAL by aldehyde dehydrogenase. Elevated levels of cytosolic DOPAL might contribute to loss of dopaminergic neurons in Parkinson disease.</abstract><subject lang="en"><genre>Keywords</genre><topic>aldehyde dehydrogenase</topic><topic>dihydroxyphenylacetaldehyde</topic><topic>dihydroxyphenylglycol</topic><topic>dopamine</topic><topic>norepinephrine</topic><topic>Parkinson disease</topic><topic>putamen</topic></subject><relatedItem type="host"><titleInfo><title>European Journal of Neurology</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">1351-5101</identifier><identifier type="eISSN">1468-1331</identifier><identifier type="DOI">10.1111/(ISSN)1468-1331</identifier><identifier type="PublisherID">ENE</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>18</number></detail><detail type="issue"><caption>no.</caption><number>5</number></detail><extent unit="pages"><start>703</start><end>710</end><total>8</total></extent></part></relatedItem><identifier type="istex">A8053DC4D0F138A958805F51B310A5D9348C2811</identifier><identifier type="DOI">10.1111/j.1468-1331.2010.03246.x</identifier><identifier type="ArticleID">ENE3246</identifier><accessCondition type="use and reproduction" contentType="copyright">No claim to original US government works. 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