Environmental neurotoxin‐induced progressive model of parkinsonism in rats
Identifieur interne : 001F51 ( Main/Corpus ); précédent : 001F50; suivant : 001F52Environmental neurotoxin‐induced progressive model of parkinsonism in rats
Auteurs : Wei-Bin Shen ; Kimberly A. Mcdowell ; Aubrey A. Siebert ; Sarah M. Clark ; Natalie V. Dugger ; Kimberly M. Valentino ; H. A. Jinnah ; Carole Sztalryd ; Paul S. Fishman ; Christopher A. Shaw ; M. Samir Jafri ; Paul J. YarowskySource :
- Annals of Neurology [ 0364-5134 ] ; 2010-07.
Abstract
Objective: Exposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant Cycas micronesica by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex. Methods: We now report that consumption of washed cycad flour pellets by Sprague‐Dawley male rats induces progressive parkinsonism. Results: Cycad‐fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad‐fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). α‐Synuclein (α‐syn; proteinase K‐resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified α‐syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and α‐syn aggregates in the SN. Interpretation: Cycad‐fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality. ANN NEUROL 2010;68:70–80
Url:
DOI: 10.1002/ana.22018
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Mcdowell</name><affiliation><mods:affiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Siebert, Aubrey A" sort="Siebert, Aubrey A" uniqKey="Siebert A" first="Aubrey A." last="Siebert">Aubrey A. Siebert</name><affiliation><mods:affiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Clark, Sarah M" sort="Clark, Sarah M" uniqKey="Clark S" first="Sarah M." last="Clark">Sarah M. Clark</name><affiliation><mods:affiliation>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Dugger, Natalie V" sort="Dugger, Natalie V" uniqKey="Dugger N" first="Natalie V." last="Dugger">Natalie V. Dugger</name><affiliation><mods:affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Valentino, Kimberly M" sort="Valentino, Kimberly M" uniqKey="Valentino K" first="Kimberly M." last="Valentino">Kimberly M. Valentino</name><affiliation><mods:affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Jinnah, H A" sort="Jinnah, H A" uniqKey="Jinnah H" first="H. A." last="Jinnah">H. A. Jinnah</name><affiliation><mods:affiliation>Department of Neurology, Emory University, Atlanta, GA</mods:affiliation></affiliation></author><author><name sortKey="Sztalryd, Carole" sort="Sztalryd, Carole" uniqKey="Sztalryd C" first="Carole" last="Sztalryd">Carole Sztalryd</name><affiliation><mods:affiliation>Department of Gerontology, University of Maryland School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Fishman, Paul S" sort="Fishman, Paul S" uniqKey="Fishman P" first="Paul S." last="Fishman">Paul S. Fishman</name><affiliation><mods:affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Maryland School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Shaw, Christopher A" sort="Shaw, Christopher A" uniqKey="Shaw C" first="Christopher A." last="Shaw">Christopher A. Shaw</name><affiliation><mods:affiliation>Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>Neuroscience Programme, University of British Columbia, Vancouver, BC, Canada</mods:affiliation></affiliation></author><author><name sortKey="Jafri, M Samir" sort="Jafri, M Samir" uniqKey="Jafri M" first="M. Samir" last="Jafri">M. Samir Jafri</name><affiliation><mods:affiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</mods:affiliation></affiliation><affiliation><mods:affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Maryland School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author><author><name sortKey="Yarowsky, Paul J" sort="Yarowsky, Paul J" uniqKey="Yarowsky P" first="Paul J." last="Yarowsky">Paul J. Yarowsky</name><affiliation><mods:affiliation>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD</mods:affiliation></affiliation><affiliation><mods:affiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</mods:affiliation></affiliation><affiliation><mods:affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</mods:affiliation></affiliation><affiliation><mods:affiliation>Program in Toxicology, University of Maryland School of Medicine, Baltimore, MD</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-07">2010-07</date><biblScope unit="volume">68</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="70">70</biblScope><biblScope unit="page" to="80">80</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">E2788F13465A8EBB5FD1DEECFBA80A1E6B264856</idno><idno type="DOI">10.1002/ana.22018</idno><idno type="ArticleID">ANA22018</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective: Exposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant Cycas micronesica by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex. Methods: We now report that consumption of washed cycad flour pellets by Sprague‐Dawley male rats induces progressive parkinsonism. Results: Cycad‐fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad‐fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). α‐Synuclein (α‐syn; proteinase K‐resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified α‐syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and α‐syn aggregates in the SN. Interpretation: Cycad‐fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality. ANN NEUROL 2010;68:70–80</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Wei‐Bin Shen PhD</name><affiliations><json:string>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD</json:string></affiliations></json:item><json:item><name>Kimberly A. McDowell BS</name><affiliations><json:string>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</json:string></affiliations></json:item><json:item><name>Aubrey A. Siebert BS</name><affiliations><json:string>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</json:string></affiliations></json:item><json:item><name>Sarah M. Clark BS</name><affiliations><json:string>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD</json:string></affiliations></json:item><json:item><name>Natalie V. Dugger BS</name><affiliations><json:string>Research Service, Maryland VA Health Care System, Baltimore, MD</json:string></affiliations></json:item><json:item><name>Kimberly M. Valentino MS</name><affiliations><json:string>Research Service, Maryland VA Health Care System, Baltimore, MD</json:string></affiliations></json:item><json:item><name>H. A. Jinnah MD, PhD</name><affiliations><json:string>Department of Neurology, Emory University, Atlanta, GA</json:string></affiliations></json:item><json:item><name>Carole Sztalryd PhD</name><affiliations><json:string>Department of Gerontology, University of Maryland School of Medicine, Baltimore, MD</json:string></affiliations></json:item><json:item><name>Paul S. Fishman MD, PhD</name><affiliations><json:string>Research Service, Maryland VA Health Care System, Baltimore, MD</json:string><json:string>Department of Neurology, University of Maryland School of Medicine, Baltimore, MD</json:string></affiliations></json:item><json:item><name>Christopher A. Shaw PhD</name><affiliations><json:string>Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada</json:string><json:string>Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada</json:string><json:string>Neuroscience Programme, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>M. Samir Jafri PhD</name><affiliations><json:string>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</json:string><json:string>Research Service, Maryland VA Health Care System, Baltimore, MD</json:string><json:string>Department of Neurology, University of Maryland School of Medicine, Baltimore, MD</json:string></affiliations></json:item><json:item><name>Paul J. Yarowsky PhD</name><affiliations><json:string>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD</json:string><json:string>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</json:string><json:string>Research Service, Maryland VA Health Care System, Baltimore, MD</json:string><json:string>Program in Toxicology, University of Maryland School of Medicine, Baltimore, MD</json:string></affiliations></json:item></author><articleId><json:string>ANA22018</json:string></articleId><language><json:string>eng</json:string></language><abstract>Objective: Exposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant Cycas micronesica by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex. Methods: We now report that consumption of washed cycad flour pellets by Sprague‐Dawley male rats induces progressive parkinsonism. Results: Cycad‐fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad‐fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). α‐Synuclein (α‐syn; proteinase K‐resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified α‐syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and α‐syn aggregates in the SN. Interpretation: Cycad‐fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality. ANN NEUROL 2010;68:70–80</abstract><qualityIndicators><score>7.82</score><pdfVersion>1.3</pdfVersion><pdfPageSize>594 x 783 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>1615</abstractCharCount><pdfWordCount>5933</pdfWordCount><pdfCharCount>36567</pdfCharCount><pdfPageCount>11</pdfPageCount><abstractWordCount>235</abstractWordCount></qualityIndicators><title>Environmental neurotoxin‐induced progressive model of parkinsonism in rats</title><genre><json:string>article</json:string></genre><host><volume>68</volume><publisherId><json:string>ANA</json:string></publisherId><pages><total>11</total><last>80</last><first>70</first></pages><issn><json:string>0364-5134</json:string></issn><issue>1</issue><subject><json:item><value>Original Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8249</json:string></eissn><title>Annals of Neurology</title><doi><json:string>10.1002/(ISSN)1531-8249</json:string></doi></host><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1002/ana.22018</json:string></doi><id>E2788F13465A8EBB5FD1DEECFBA80A1E6B264856</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/E2788F13465A8EBB5FD1DEECFBA80A1E6B264856/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/E2788F13465A8EBB5FD1DEECFBA80A1E6B264856/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/E2788F13465A8EBB5FD1DEECFBA80A1E6B264856/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Environmental neurotoxin‐induced progressive model of parkinsonism in rats</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2010</date></publicationStmt><notesStmt><note>Veteran's Affairs</note><note>National Institutes of Health</note><note>National Institute of Environmental Health Sciences training grant</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Environmental neurotoxin‐induced progressive model of parkinsonism in rats</title><author><persName><forename type="first">Wei‐Bin</forename><surname>Shen</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD</affiliation></author><author><persName><forename type="first">Kimberly A.</forename><surname>McDowell</surname></persName><roleName type="degree">BS</roleName><affiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</affiliation></author><author><persName><forename type="first">Aubrey A.</forename><surname>Siebert</surname></persName><roleName type="degree">BS</roleName><affiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</affiliation></author><author><persName><forename type="first">Sarah M.</forename><surname>Clark</surname></persName><roleName type="degree">BS</roleName><affiliation>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD</affiliation></author><author><persName><forename type="first">Natalie V.</forename><surname>Dugger</surname></persName><roleName type="degree">BS</roleName><affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</affiliation></author><author><persName><forename type="first">Kimberly M.</forename><surname>Valentino</surname></persName><roleName type="degree">MS</roleName><affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</affiliation></author><author><persName><forename type="first">H. A.</forename><surname>Jinnah</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Emory University, Atlanta, GA</affiliation></author><author><persName><forename type="first">Carole</forename><surname>Sztalryd</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Gerontology, University of Maryland School of Medicine, Baltimore, MD</affiliation></author><author><persName><forename type="first">Paul S.</forename><surname>Fishman</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</affiliation><affiliation>Department of Neurology, University of Maryland School of Medicine, Baltimore, MD</affiliation></author><author><persName><forename type="first">Christopher A.</forename><surname>Shaw</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada</affiliation><affiliation>Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada</affiliation><affiliation>Neuroscience Programme, University of British Columbia, Vancouver, BC, Canada</affiliation></author><author><persName><forename type="first">M. Samir</forename><surname>Jafri</surname></persName><roleName type="degree">PhD</roleName><affiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</affiliation><affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</affiliation><affiliation>Department of Neurology, University of Maryland School of Medicine, Baltimore, MD</affiliation></author><author><persName><forename type="first">Paul J.</forename><surname>Yarowsky</surname></persName><roleName type="degree">PhD</roleName><note type="correspondence"><p>Correspondence: Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201</p></note><affiliation>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD</affiliation><affiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</affiliation><affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</affiliation><affiliation>Program in Toxicology, University of Maryland School of Medicine, Baltimore, MD</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-07"></date><biblScope unit="volume">68</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="70">70</biblScope><biblScope unit="page" to="80">80</biblScope></imprint></monogr><idno type="istex">E2788F13465A8EBB5FD1DEECFBA80A1E6B264856</idno><idno type="DOI">10.1002/ana.22018</idno><idno type="ArticleID">ANA22018</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Objective: Exposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant Cycas micronesica by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex. Methods: We now report that consumption of washed cycad flour pellets by Sprague‐Dawley male rats induces progressive parkinsonism. Results: Cycad‐fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad‐fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). α‐Synuclein (α‐syn; proteinase K‐resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified α‐syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and α‐syn aggregates in the SN. Interpretation: Cycad‐fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality. ANN NEUROL 2010;68:70–80</p></abstract><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Original Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2008-10-16">Received</change><change when="2010-02-26">Registration</change><change when="2010-07">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/E2788F13465A8EBB5FD1DEECFBA80A1E6B264856/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>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8249</doi><issn type="print">0364-5134</issn><issn type="electronic">1531-8249</issn><idGroup><id type="product" value="ANA"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="ANNALS OF NEUROLOGY">Annals of Neurology</title><title type="short">Ann Neurol.</title></titleGroup></publicationMeta><publicationMeta level="part" position="10"><doi origin="wiley" registered="yes">10.1002/ana.v68:1</doi><numberingGroup><numbering type="journalVolume" number="68">68</numbering><numbering type="journalIssue">1</numbering></numberingGroup><coverDate startDate="2010-07">July 2010</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="150" status="forIssue"><doi origin="wiley" registered="yes">10.1002/ana.22018</doi><idGroup><id type="unit" value="ANA22018"></id></idGroup><countGroup><count type="pageTotal" number="11"></count></countGroup><titleGroup><title type="articleCategory">Original Article</title><title type="tocHeading1">Original Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2010 American Neurological Association</copyright><eventGroup><event type="manuscriptReceived" date="2008-10-16"></event><event type="manuscriptRevised" date="2010-02-25"></event><event type="manuscriptAccepted" date="2010-02-26"></event><event type="publishedOnlineAccepted" date="2010-03-15"></event><event type="firstOnline" date="2010-03-15"></event><event type="publishedOnlineFinalForm" date="2010-06-25"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.15 mode:FullText source:FullText result:FullText" date="2010-07-21"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-03"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst">70</numbering><numbering type="pageLast">80</numbering></numberingGroup><correspondenceTo>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:ANA.ANA22018.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="6"></count><count type="tableTotal" number="0"></count><count type="referenceTotal" number="46"></count><count type="wordTotal" number="6496"></count></countGroup><titleGroup><title type="main" xml:lang="en">Environmental neurotoxin‐induced progressive model of parkinsonism in rats</title><title type="short" xml:lang="en">Cycad‐Induced Parkinsonism</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Wei‐Bin</givenNames><familyName>Shen</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Kimberly A.</givenNames><familyName>McDowell</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Aubrey A.</givenNames><familyName>Siebert</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Sarah M.</givenNames><familyName>Clark</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Natalie V.</givenNames><familyName>Dugger</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Kimberly M.</givenNames><familyName>Valentino</familyName><degrees>MS</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af4"><personName><givenNames>H. A.</givenNames><familyName>Jinnah</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Carole</givenNames><familyName>Sztalryd</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af3 #af6"><personName><givenNames>Paul S.</givenNames><familyName>Fishman</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af7 #af8 #af9"><personName><givenNames>Christopher A.</givenNames><familyName>Shaw</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af2 #af3 #af6"><personName><givenNames>M. Samir</givenNames><familyName>Jafri</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af1 #af2 #af3 #af10" corresponding="yes"><personName><givenNames>Paul J.</givenNames><familyName>Yarowsky</familyName><degrees>PhD</degrees></personName><contactDetails><email>pyarowsky@som.umaryland.edu</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Emory University, Atlanta, GA</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="US" type="organization"><unparsedAffiliation>Department of Gerontology, University of Maryland School of Medicine, Baltimore, MD</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, University of Maryland School of Medicine, Baltimore, MD</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="CA" type="organization"><unparsedAffiliation>Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="CA" type="organization"><unparsedAffiliation>Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="CA" type="organization"><unparsedAffiliation>Neuroscience Programme, University of British Columbia, Vancouver, BC, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="US" type="organization"><unparsedAffiliation>Program in Toxicology, University of Maryland School of Medicine, Baltimore, MD</unparsedAffiliation></affiliation></affiliationGroup><fundingInfo><fundingAgency>Veteran's Affairs</fundingAgency></fundingInfo><fundingInfo><fundingAgency>National Institutes of Health</fundingAgency></fundingInfo><fundingInfo><fundingAgency>National Institute of Environmental Health Sciences training grant</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><section xml:id="abs1-1"><title type="main">Objective</title><p>Exposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant <i>Cycas micronesica</i> by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex.</p></section><section xml:id="abs1-2"><title type="main">Methods</title><p>We now report that consumption of washed cycad flour pellets by Sprague‐Dawley male rats induces progressive parkinsonism.</p></section><section xml:id="abs1-3"><title type="main">Results</title><p>Cycad‐fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad‐fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). α‐Synuclein (α‐syn; proteinase K‐resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified α‐syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and α‐syn aggregates in the SN.</p></section><section xml:id="abs1-4"><title type="main">Interpretation</title><p>Cycad‐fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality. ANN NEUROL 2010;68:70–80</p></section></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Environmental neurotoxin‐induced progressive model of parkinsonism in rats</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Cycad‐Induced Parkinsonism</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Environmental neurotoxin‐induced progressive model of parkinsonism in rats</title></titleInfo><name type="personal"><namePart type="given">Wei‐Bin</namePart><namePart type="family">Shen</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kimberly A.</namePart><namePart type="family">McDowell</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Aubrey A.</namePart><namePart type="family">Siebert</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sarah M.</namePart><namePart type="family">Clark</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Natalie V.</namePart><namePart type="family">Dugger</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kimberly M.</namePart><namePart type="family">Valentino</namePart><namePart type="termsOfAddress">MS</namePart><affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">H. A.</namePart><namePart type="family">Jinnah</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, Emory University, Atlanta, GA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Carole</namePart><namePart type="family">Sztalryd</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Gerontology, University of Maryland School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Paul S.</namePart><namePart type="family">Fishman</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</affiliation><affiliation>Department of Neurology, University of Maryland School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christopher A.</namePart><namePart type="family">Shaw</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada</affiliation><affiliation>Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada</affiliation><affiliation>Neuroscience Programme, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M. Samir</namePart><namePart type="family">Jafri</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</affiliation><affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</affiliation><affiliation>Department of Neurology, University of Maryland School of Medicine, Baltimore, MD</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Paul J.</namePart><namePart type="family">Yarowsky</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD</affiliation><affiliation>Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</affiliation><affiliation>Research Service, Maryland VA Health Care System, Baltimore, MD</affiliation><affiliation>Program in Toxicology, University of Maryland School of Medicine, Baltimore, MD</affiliation><description>Correspondence: Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2010-07</dateIssued><dateCaptured encoding="w3cdtf">2008-10-16</dateCaptured><dateValid encoding="w3cdtf">2010-02-26</dateValid><copyrightDate encoding="w3cdtf">2010</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">6</extent><extent unit="references">46</extent><extent unit="words">6496</extent></physicalDescription><abstract lang="en">Objective: Exposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant Cycas micronesica by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex. Methods: We now report that consumption of washed cycad flour pellets by Sprague‐Dawley male rats induces progressive parkinsonism. Results: Cycad‐fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad‐fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). α‐Synuclein (α‐syn; proteinase K‐resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified α‐syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and α‐syn aggregates in the SN. Interpretation: Cycad‐fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality. ANN NEUROL 2010;68:70–80</abstract><note type="funding">Veteran's Affairs</note><note type="funding">National Institutes of Health</note><note type="funding">National Institute of Environmental Health Sciences training grant</note><relatedItem type="host"><titleInfo><title>Annals of Neurology</title></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>68</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>70</start><end>80</end><total>11</total></extent></part></relatedItem><identifier type="istex">E2788F13465A8EBB5FD1DEECFBA80A1E6B264856</identifier><identifier type="DOI">10.1002/ana.22018</identifier><identifier type="ArticleID">ANA22018</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2010 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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