Environmental neurotoxin‐induced progressive model of parkinsonism in rats
Identifieur interne : 000728 ( Main/Exploration ); précédent : 000727; suivant : 000729Environmental neurotoxin‐induced progressive model of parkinsonism in rats
Auteurs : Wei-Bin Shen [États-Unis] ; Kimberly A. Mcdowell [États-Unis] ; Aubrey A. Siebert [États-Unis] ; Sarah M. Clark [États-Unis] ; Natalie V. Dugger [États-Unis] ; Kimberly M. Valentino [États-Unis] ; H. A. Jinnah [États-Unis] ; Carole Sztalryd [États-Unis] ; Paul S. Fishman [États-Unis] ; Christopher A. Shaw [Canada] ; M. Samir Jafri [États-Unis] ; Paul J. Yarowsky [États-Unis]Source :
- 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
Affiliations:
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Jinnah</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Géorgie (États-Unis)</region></placeName><wicri:cityArea>Department of Neurology, Emory University, Atlanta</wicri:cityArea></affiliation></author><author><name sortKey="Sztalryd, Carole" sort="Sztalryd, Carole" uniqKey="Sztalryd C" first="Carole" last="Sztalryd">Carole Sztalryd</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Department of Gerontology, University of Maryland School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Fishman, Paul S" sort="Fishman, Paul S" uniqKey="Fishman P" first="Paul S." last="Fishman">Paul S. 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Shaw</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Experimental Medicine, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Neuroscience Programme, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></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 wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Program in Neuroscience, University of Maryland School of Medicine, Baltimore</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Research Service, Maryland VA Health Care System, Baltimore</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Department of Neurology, University of Maryland School of Medicine, Baltimore</wicri:cityArea></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 wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Program in Neuroscience, University of Maryland School of Medicine, Baltimore</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Research Service, Maryland VA Health Care System, Baltimore</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Program in Toxicology, University of Maryland School of Medicine, Baltimore</wicri:cityArea></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><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Géorgie (États-Unis)</li><li>Maryland</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Shen, Wei In" sort="Shen, Wei In" uniqKey="Shen W" first="Wei-Bin" last="Shen">Wei-Bin Shen</name></region><name sortKey="Clark, Sarah M" sort="Clark, Sarah M" uniqKey="Clark S" first="Sarah M." last="Clark">Sarah M. Clark</name><name sortKey="Dugger, Natalie V" sort="Dugger, Natalie V" uniqKey="Dugger N" first="Natalie V." last="Dugger">Natalie V. Dugger</name><name sortKey="Fishman, Paul S" sort="Fishman, Paul S" uniqKey="Fishman P" first="Paul S." last="Fishman">Paul S. Fishman</name><name sortKey="Fishman, Paul S" sort="Fishman, Paul S" uniqKey="Fishman P" first="Paul S." last="Fishman">Paul S. Fishman</name><name sortKey="Jafri, M Samir" sort="Jafri, M Samir" uniqKey="Jafri M" first="M. Samir" last="Jafri">M. Samir Jafri</name><name sortKey="Jafri, M Samir" sort="Jafri, M Samir" uniqKey="Jafri M" first="M. Samir" last="Jafri">M. Samir Jafri</name><name sortKey="Jafri, M Samir" sort="Jafri, M Samir" uniqKey="Jafri M" first="M. Samir" last="Jafri">M. Samir Jafri</name><name sortKey="Jinnah, H A" sort="Jinnah, H A" uniqKey="Jinnah H" first="H. A." last="Jinnah">H. A. Jinnah</name><name sortKey="Mcdowell, Kimberly A" sort="Mcdowell, Kimberly A" uniqKey="Mcdowell K" first="Kimberly A." last="Mcdowell">Kimberly A. Mcdowell</name><name sortKey="Siebert, Aubrey A" sort="Siebert, Aubrey A" uniqKey="Siebert A" first="Aubrey A." last="Siebert">Aubrey A. Siebert</name><name sortKey="Sztalryd, Carole" sort="Sztalryd, Carole" uniqKey="Sztalryd C" first="Carole" last="Sztalryd">Carole Sztalryd</name><name sortKey="Valentino, Kimberly M" sort="Valentino, Kimberly M" uniqKey="Valentino K" first="Kimberly M." last="Valentino">Kimberly M. Valentino</name><name sortKey="Yarowsky, Paul J" sort="Yarowsky, Paul J" uniqKey="Yarowsky P" first="Paul J." last="Yarowsky">Paul J. Yarowsky</name><name sortKey="Yarowsky, Paul J" sort="Yarowsky, Paul J" uniqKey="Yarowsky P" first="Paul J." last="Yarowsky">Paul J. Yarowsky</name><name sortKey="Yarowsky, Paul J" sort="Yarowsky, Paul J" uniqKey="Yarowsky P" first="Paul J." last="Yarowsky">Paul J. Yarowsky</name><name sortKey="Yarowsky, Paul J" sort="Yarowsky, Paul J" uniqKey="Yarowsky P" first="Paul J." last="Yarowsky">Paul J. Yarowsky</name></country><country name="Canada"><noRegion><name sortKey="Shaw, Christopher A" sort="Shaw, Christopher A" uniqKey="Shaw C" first="Christopher A." last="Shaw">Christopher A. Shaw</name></noRegion><name sortKey="Shaw, Christopher A" sort="Shaw, Christopher A" uniqKey="Shaw C" first="Christopher A." last="Shaw">Christopher A. Shaw</name><name sortKey="Shaw, Christopher A" sort="Shaw, Christopher A" uniqKey="Shaw C" first="Christopher A." last="Shaw">Christopher A. Shaw</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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