Viral-toxin interactions and Parkinson’s disease: poly(I:C) priming enhanced the neurodegenerative effects of paraquat
Identifieur interne : 001091 ( Main/Exploration ); précédent : 001090; suivant : 001092Viral-toxin interactions and Parkinson’s disease: poly(I:C) priming enhanced the neurodegenerative effects of paraquat
Auteurs : Jessica Bobyn [Canada] ; Emily N. Mangano [Canada] ; Anusha Gandhi [Canada] ; Eric Nelson [Canada] ; Kerry Moloney [Canada] ; Melanie Clarke [Canada] ; Shawn Hayley [Canada]Source :
- Journal of Neuroinflammation [ 1742-2094 ] ; 2012.
Abstract
Parkinson’s disease (PD) has been linked with exposure to a variety of environmental and immunological insults (for example, infectious pathogens) in which inflammatory and oxidative processes seem to be involved. In particular, epidemiological studies have found that pesticide exposure and infections may be linked with the incidence of PD. The present study sought to determine whether exposure to a viral mimic prior to exposure to pesticides would exacerbate PD-like pathology.
Mice received a supra-nigral infusion of 5 μg of the double-stranded RNA viral analog, polyinosinic: polycytidylic acid (poly(I:C)), followed 2, 7 or 14 days later by administration of the pesticide, paraquat (nine 10 mg/kg injections over three weeks).
As hypothesized, poly(I:C) pre-treatment enhanced dopamine (DA) neuron loss in the substantia nigra pars compacta elicited by subsequent paraquat treatment. The augmented neuronal loss was accompanied by robust signs of microglial activation, and by increased expression of the catalytic subunit (gp91) of the NADPH oxidase oxidative stress enzyme. However, the paraquat and poly(I:C) treatments did not appreciably affect home-cage activity, striatal DA terminals, or subventricular neurogenesis.
These findings suggest that viral agents can sensitize microglial-dependent inflammatory responses, thereby rendering nigral DA neurons vulnerable to further environmental toxin exposure.
Url:
DOI: 10.1186/1742-2094-9-86
PubMed: 22559812
PubMed Central: 3464726
Affiliations:
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Mangano</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Gandhi, Anusha" sort="Gandhi, Anusha" uniqKey="Gandhi A" first="Anusha" last="Gandhi">Anusha Gandhi</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Nelson, Eric" sort="Nelson, Eric" uniqKey="Nelson E" first="Eric" last="Nelson">Eric Nelson</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Moloney, Kerry" sort="Moloney, Kerry" uniqKey="Moloney K" first="Kerry" last="Moloney">Kerry Moloney</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Clarke, Melanie" sort="Clarke, Melanie" uniqKey="Clarke M" first="Melanie" last="Clarke">Melanie Clarke</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Hayley, Shawn" sort="Hayley, Shawn" uniqKey="Hayley S" first="Shawn" last="Hayley">Shawn Hayley</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22559812</idno><idno type="pmc">3464726</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464726</idno><idno type="RBID">PMC:3464726</idno><idno type="doi">10.1186/1742-2094-9-86</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000500</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000500</idno><idno type="wicri:Area/Pmc/Curation">000500</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000500</idno><idno type="wicri:Area/Pmc/Checkpoint">000740</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000740</idno><idno type="wicri:Area/Ncbi/Merge">001141</idno><idno type="wicri:Area/Ncbi/Curation">001141</idno><idno type="wicri:Area/Ncbi/Checkpoint">001141</idno><idno type="wicri:Area/Main/Merge">001110</idno><idno type="wicri:Area/Main/Curation">001091</idno><idno type="wicri:Area/Main/Exploration">001091</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Viral-toxin interactions and Parkinson’s disease: poly(I:C) priming enhanced the neurodegenerative effects of paraquat</title><author><name sortKey="Bobyn, Jessica" sort="Bobyn, Jessica" uniqKey="Bobyn J" first="Jessica" last="Bobyn">Jessica Bobyn</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Mangano, Emily N" sort="Mangano, Emily N" uniqKey="Mangano E" first="Emily N" last="Mangano">Emily N. Mangano</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Gandhi, Anusha" sort="Gandhi, Anusha" uniqKey="Gandhi A" first="Anusha" last="Gandhi">Anusha Gandhi</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Nelson, Eric" sort="Nelson, Eric" uniqKey="Nelson E" first="Eric" last="Nelson">Eric Nelson</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Moloney, Kerry" sort="Moloney, Kerry" uniqKey="Moloney K" first="Kerry" last="Moloney">Kerry Moloney</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Clarke, Melanie" sort="Clarke, Melanie" uniqKey="Clarke M" first="Melanie" last="Clarke">Melanie Clarke</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author><author><name sortKey="Hayley, Shawn" sort="Hayley, Shawn" uniqKey="Hayley S" first="Shawn" last="Hayley">Shawn Hayley</name><affiliation wicri:level="1"><nlm:aff id="I1">Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6</wicri:regionArea><wicri:noRegion>K1S 5B6</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of Neuroinflammation</title><idno type="eISSN">1742-2094</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title><bold>Background</bold></title><p>Parkinson’s disease (PD) has been linked with exposure to a variety of environmental and immunological insults (for example, infectious pathogens) in which inflammatory and oxidative processes seem to be involved. In particular, epidemiological studies have found that pesticide exposure and infections may be linked with the incidence of PD. The present study sought to determine whether exposure to a viral mimic prior to exposure to pesticides would exacerbate PD-like pathology.</p></sec><sec><title><bold>Methods</bold></title><p>Mice received a supra-nigral infusion of 5 μg of the double-stranded RNA viral analog, polyinosinic: polycytidylic acid (poly(I:C)), followed 2, 7 or 14 days later by administration of the pesticide, paraquat (nine 10 mg/kg injections over three weeks).</p></sec><sec><title><bold>Results</bold></title><p>As hypothesized, poly(I:C) pre-treatment enhanced dopamine (DA) neuron loss in the substantia nigra pars compacta elicited by subsequent paraquat treatment. The augmented neuronal loss was accompanied by robust signs of microglial activation, and by increased expression of the catalytic subunit (gp91) of the NADPH oxidase oxidative stress enzyme. However, the paraquat and poly(I:C) treatments did not appreciably affect home-cage activity, striatal DA terminals, or subventricular neurogenesis.</p></sec><sec><title><bold>Conclusions</bold></title><p>These findings suggest that viral agents can sensitize microglial-dependent inflammatory responses, thereby rendering nigral DA neurons vulnerable to further environmental toxin exposure.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Lev, N" uniqKey="Lev N">N Lev</name></author><author><name sortKey="Melamed, E" uniqKey="Melamed E">E Melamed</name></author><author><name sortKey="Offen, D" uniqKey="Offen D">D Offen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mccoy, Mk" uniqKey="Mccoy M">MK McCoy</name></author><author><name sortKey="Cookson, Mr" uniqKey="Cookson M">MR Cookson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcnaught, Ks" 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Greenamyre</name></author><author><name sortKey="Miller, Gw" uniqKey="Miller G">GW Miller</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Bobyn, Jessica" sort="Bobyn, Jessica" uniqKey="Bobyn J" first="Jessica" last="Bobyn">Jessica Bobyn</name></noRegion><name sortKey="Clarke, Melanie" sort="Clarke, Melanie" uniqKey="Clarke M" first="Melanie" last="Clarke">Melanie Clarke</name><name sortKey="Gandhi, Anusha" sort="Gandhi, Anusha" uniqKey="Gandhi A" first="Anusha" last="Gandhi">Anusha Gandhi</name><name sortKey="Hayley, Shawn" sort="Hayley, Shawn" uniqKey="Hayley S" first="Shawn" last="Hayley">Shawn Hayley</name><name sortKey="Mangano, Emily N" sort="Mangano, Emily N" uniqKey="Mangano E" first="Emily N" last="Mangano">Emily N. Mangano</name><name sortKey="Moloney, Kerry" sort="Moloney, Kerry" uniqKey="Moloney K" first="Kerry" last="Moloney">Kerry Moloney</name><name sortKey="Nelson, Eric" sort="Nelson, Eric" uniqKey="Nelson E" first="Eric" last="Nelson">Eric Nelson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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