ParkinsonCanadaV1, Pmc, Corpus, bibRecord, 000414

Environmental neurotoxin-induced progressive model of parkinsonism in rats

Identifieur interne : 000414 ( Pmc/Corpus ); précédent : 000413; suivant : 000415

Environmental 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. Yarowsky

Source :

Annals of neurology [ 0364-5134 ] ; 2010.

RBID : PMC:2988442

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 (ALS/PDC).

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 two to three 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 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 substantia nigra and the striatum, an organic extract of cycad causes a selective loss of DA neurons and α-synuclein aggregates in the substantia nigra.

Interpretation

Cycad-fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988442

DOI: 10.1002/ana.22018
PubMed: 20582986
PubMed Central: 2988442

Links to Exploration step

PMC:2988442

Le document en format XML

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<author><name sortKey="Shen, Wei Bin" sort="Shen, Wei Bin" uniqKey="Shen W" first="Wei-Bin" last="Shen">Wei-Bin Shen</name>
<affiliation><nlm:aff id="A1">Dept. of Pharmacology & Experimental Therapeutics, Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD</nlm:aff>
</affiliation>
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<author><name sortKey="Mcdowell, Kimberly A" sort="Mcdowell, Kimberly A" uniqKey="Mcdowell K" first="Kimberly A." last="Mcdowell">Kimberly A. Mcdowell</name>
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<author><name sortKey="Siebert, Aubrey A" sort="Siebert, Aubrey A" uniqKey="Siebert A" first="Aubrey A." last="Siebert">Aubrey A. Siebert</name>
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<author><name sortKey="Valentino, Kimberly M" sort="Valentino, Kimberly M" uniqKey="Valentino K" first="Kimberly M." last="Valentino">Kimberly M. Valentino</name>
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<author><name sortKey="Sztalryd, Carole" sort="Sztalryd, Carole" uniqKey="Sztalryd C" first="Carole" last="Sztalryd">Carole Sztalryd</name>
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<author><name sortKey="Fishman, Paul S" sort="Fishman, Paul S" uniqKey="Fishman P" first="Paul S." last="Fishman">Paul S. Fishman</name>
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</affiliation>
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<author><name sortKey="Shaw, Christopher A" sort="Shaw, Christopher A" uniqKey="Shaw C" first="Christopher A." last="Shaw">Christopher A. Shaw</name>
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</affiliation>
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<author><name sortKey="Jafri, M Samir" sort="Jafri, M Samir" uniqKey="Jafri M" first="M. Samir" last="Jafri">M. Samir Jafri</name>
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<affiliation><nlm:aff id="A7">Dept. of Neurology, University of Maryland School of Medicine, Baltimore, MD</nlm:aff>
</affiliation>
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<author><name sortKey="Yarowsky, Paul J" sort="Yarowsky, Paul J" uniqKey="Yarowsky P" first="Paul J." last="Yarowsky">Paul J. Yarowsky</name>
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</affiliation>
<affiliation><nlm:aff id="A2">Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</nlm:aff>
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<affiliation><nlm:aff id="A3">Research Service, Maryland VA Health Care System, Baltimore, MD</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Program in Toxicology, University of Maryland School of Medicine, Baltimore, MD</nlm:aff>
</affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Environmental neurotoxin-induced progressive model of parkinsonism in rats</title>
<author><name sortKey="Shen, Wei Bin" sort="Shen, Wei Bin" uniqKey="Shen W" first="Wei-Bin" last="Shen">Wei-Bin Shen</name>
<affiliation><nlm:aff id="A1">Dept. of Pharmacology & Experimental Therapeutics, Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD</nlm:aff>
</affiliation>
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<author><name sortKey="Mcdowell, Kimberly A" sort="Mcdowell, Kimberly A" uniqKey="Mcdowell K" first="Kimberly A." last="Mcdowell">Kimberly A. Mcdowell</name>
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<author><name sortKey="Siebert, Aubrey A" sort="Siebert, Aubrey A" uniqKey="Siebert A" first="Aubrey A." last="Siebert">Aubrey A. Siebert</name>
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</affiliation>
</author>
<author><name sortKey="Clark, Sarah M" sort="Clark, Sarah M" uniqKey="Clark S" first="Sarah M." last="Clark">Sarah M. Clark</name>
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</affiliation>
</author>
<author><name sortKey="Dugger, Natalie V" sort="Dugger, Natalie V" uniqKey="Dugger N" first="Natalie V." last="Dugger">Natalie V. Dugger</name>
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</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><nlm:aff id="A3">Research Service, Maryland VA Health Care System, Baltimore, MD</nlm:aff>
</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><nlm:aff id="A5">Dept. of Neurology, Dept. of Neurology, Emory University, Atlanta, GA</nlm:aff>
</affiliation>
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<author><name sortKey="Sztalryd, Carole" sort="Sztalryd, Carole" uniqKey="Sztalryd C" first="Carole" last="Sztalryd">Carole Sztalryd</name>
<affiliation><nlm:aff id="A6">Dept. of Gerontology, University of Maryland School of Medicine, Baltimore, MD</nlm:aff>
</affiliation>
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<author><name sortKey="Fishman, Paul S" sort="Fishman, Paul S" uniqKey="Fishman P" first="Paul S." last="Fishman">Paul S. Fishman</name>
<affiliation><nlm:aff id="A3">Research Service, Maryland VA Health Care System, Baltimore, MD</nlm:aff>
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<affiliation><nlm:aff id="A7">Dept. of Neurology, University of Maryland School of Medicine, Baltimore, MD</nlm:aff>
</affiliation>
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<author><name sortKey="Shaw, Christopher A" sort="Shaw, Christopher A" uniqKey="Shaw C" first="Christopher A." last="Shaw">Christopher A. Shaw</name>
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</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><nlm:aff id="A2">Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Research Service, Maryland VA Health Care System, Baltimore, MD</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A7">Dept. of Neurology, University of Maryland School of Medicine, Baltimore, MD</nlm:aff>
</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><nlm:aff id="A1">Dept. of Pharmacology & Experimental Therapeutics, Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A3">Research Service, Maryland VA Health Care System, Baltimore, MD</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Program in Toxicology, University of Maryland School of Medicine, Baltimore, MD</nlm:aff>
</affiliation>
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<series><title level="j">Annals of neurology</title>
<idno type="ISSN">0364-5134</idno>
<idno type="eISSN">1531-8249</idno>
<imprint><date when="2010">2010</date>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Objective</title>
<p id="P2">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, <italic>Cycas micronesica</italic>
, by the Chamorro population of Guam and the development of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC).</p>
</sec>
<sec sec-type="methods" id="S2"><title>Methods</title>
<p id="P3">We now report that consumption of washed cycad flour pellets by Sprague-Dawley male rats induces progressive parkinsonism.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P4">Cycad-fed rats displayed motor abnormalities after two to three 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 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 substantia nigra and the striatum, an organic extract of cycad causes a selective loss of DA neurons and α-synuclein aggregates in the substantia nigra.</p>
</sec>
<sec id="S4"><title>Interpretation</title>
<p id="P5">Cycad-fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <pmc-dir>properties manuscript</pmc-dir>
  <front><journal-meta><journal-id journal-id-type="nlm-journal-id">7707449</journal-id>
<journal-id journal-id-type="pubmed-jr-id">656</journal-id>
<journal-id journal-id-type="nlm-ta">Ann Neurol</journal-id>
<journal-title>Annals of neurology</journal-title>
<issn pub-type="ppub">0364-5134</issn>
<issn pub-type="epub">1531-8249</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">20582986</article-id>
<article-id pub-id-type="pmc">2988442</article-id>
<article-id pub-id-type="doi">10.1002/ana.22018</article-id>
<article-id pub-id-type="manuscript">NIHMS220395</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Environmental neurotoxin-induced progressive model of parkinsonism in rats</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Shen</surname>
<given-names>Wei-Bin</given-names>
</name>
<degrees>Ph.D.</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McDowell</surname>
<given-names>Kimberly A.</given-names>
</name>
<degrees>B.S.</degrees>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Siebert</surname>
<given-names>Aubrey A.</given-names>
</name>
<degrees>B.S.</degrees>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Clark</surname>
<given-names>Sarah M.</given-names>
</name>
<degrees>B.S.</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dugger</surname>
<given-names>Natalie V.</given-names>
</name>
<degrees>B.S.</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Valentino</surname>
<given-names>Kimberly M.</given-names>
</name>
<degrees>M.S.</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jinnah</surname>
<given-names>H. A.</given-names>
</name>
<degrees>M.D., Ph.D.</degrees>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sztalryd</surname>
<given-names>Carole</given-names>
</name>
<degrees>Ph.D.</degrees>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fishman</surname>
<given-names>Paul S.</given-names>
</name>
<degrees>M.D., Ph.D.</degrees>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shaw</surname>
<given-names>Christopher A.</given-names>
</name>
<degrees>Ph.D.</degrees>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jafri</surname>
<given-names>M. Samir</given-names>
</name>
<degrees>Ph.D.</degrees>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yarowsky</surname>
<given-names>Paul J.</given-names>
</name>
<degrees>Ph.D.</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Dept. of Pharmacology & Experimental Therapeutics, Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD</aff>
<aff id="A2"><label>2</label>
Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD</aff>
<aff id="A3"><label>3</label>
Research Service, Maryland VA Health Care System, Baltimore, MD</aff>
<aff id="A4"><label>4</label>
Program in Toxicology, University of Maryland School of Medicine, Baltimore, MD</aff>
<aff id="A5"><label>5</label>
Dept. of Neurology, Dept. of Neurology, Emory University, Atlanta, GA</aff>
<aff id="A6"><label>6</label>
Dept. of Gerontology, University of Maryland School of Medicine, Baltimore, MD</aff>
<aff id="A7"><label>7</label>
Dept. of Neurology, University of Maryland School of Medicine, Baltimore, MD</aff>
<aff id="A8"><label>8</label>
Depts. of Ophthalmology and Visual Sciences and Experimental Medicine, and Neuroscience Programme, University of British Columbia, Vancouver, BC, Canada</aff>
<author-notes><corresp id="cor1">Correspondence to: Dr. Paul Yarowsky, Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201, <email>pyarowsky@som.umaryland.edu</email>
</corresp>
<fn id="FN1" fn-type="equal"><label>*</label>
<p id="P1">Contributed equally</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>10</day>
<month>11</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="ppub"><month>7</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>7</month>
<year>2011</year>
</pub-date>
<volume>68</volume>
<issue>1</issue>
<fpage>70</fpage>
<lpage>80</lpage>
<abstract><sec id="S1"><title>Objective</title>
<p id="P2">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, <italic>Cycas micronesica</italic>
, by the Chamorro population of Guam and the development of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC).</p>
</sec>
<sec sec-type="methods" id="S2"><title>Methods</title>
<p id="P3">We now report that consumption of washed cycad flour pellets by Sprague-Dawley male rats induces progressive parkinsonism.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P4">Cycad-fed rats displayed motor abnormalities after two to three 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 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 substantia nigra and the striatum, an organic extract of cycad causes a selective loss of DA neurons and α-synuclein aggregates in the substantia nigra.</p>
</sec>
<sec id="S4"><title>Interpretation</title>
<p id="P5">Cycad-fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality.</p>
</sec>
</abstract>
<kwd-group><kwd>α-synuclein</kwd>
<kwd>progressive neurodegeneration</kwd>
<kwd>cycad neurotoxins</kwd>
</kwd-group>
<contract-num rid="NS1">R01 NS051723-05
				||NS</contract-num>
<contract-num rid="NS1">R01 NS040470-09
				||NS</contract-num>
<contract-num rid="DK1">R01 DK075017-04
				||DK</contract-num>
<contract-sponsor id="NS1">National Institute of Neurological Disorders and Stroke  : NINDS</contract-sponsor>
<contract-sponsor id="DK1">National Institute of Diabetes and Digestive and Kidney Diseases  : NIDDK</contract-sponsor>
</article-meta>
</front>
</pmc>
</record>

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	La maladie de Parkinson au Canada (serveur d'exploration)
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Environmental neurotoxin-induced progressive model of parkinsonism in rats

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