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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Dopamine transporter <italic>SLC6A3</italic> genotype affects cortico-striatal activity of set-shifts in Parkinson’s disease</title><author><name sortKey="Habak, Claudine" sort="Habak, Claudine" uniqKey="Habak C" first="Claudine" last="Habak">Claudine Habak</name><affiliation><nlm:aff id="awu251-AFF1">1 Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal, Montréal, Québec, H3W 1W5, Canada</nlm:aff></affiliation></author><author><name sortKey="Noreau, Anne" sort="Noreau, Anne" uniqKey="Noreau A" first="Anne" last="Noreau">Anne Noreau</name><affiliation><nlm:aff id="awu251-AFF2">2 Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Québec, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="awu251-AFF3">3 Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada</nlm:aff></affiliation></author><author><name sortKey="Nagano Saito, Atsuko" sort="Nagano Saito, Atsuko" uniqKey="Nagano Saito A" first="Atsuko" last="Nagano-Saito">Atsuko Nagano-Saito</name><affiliation><nlm:aff id="awu251-AFF1">1 Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal, Montréal, Québec, H3W 1W5, Canada</nlm:aff></affiliation></author><author><name sortKey="Mejia Constain, Beatriz" sort="Mejia Constain, Beatriz" uniqKey="Mejia Constain B" first="Beatriz" last="Mejía-Constaín">Beatriz Mejía-Constaín</name><affiliation><nlm:aff id="awu251-AFF1">1 Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal, Montréal, Québec, H3W 1W5, Canada</nlm:aff></affiliation></author><author><name sortKey="Degroot, Clotilde" sort="Degroot, Clotilde" uniqKey="Degroot C" first="Clotilde" last="Degroot">Clotilde Degroot</name><affiliation><nlm:aff id="awu251-AFF1">1 Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal, Montréal, Québec, H3W 1W5, Canada</nlm:aff></affiliation></author><author><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><affiliation><nlm:aff id="awu251-AFF4">4 Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Chouinard, Sylvain" sort="Chouinard, Sylvain" uniqKey="Chouinard S" first="Sylvain" last="Chouinard">Sylvain Chouinard</name><affiliation><nlm:aff id="awu251-AFF2">2 Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Québec, Canada</nlm:aff></affiliation></author><author><name sortKey="Lafontaine, Anne Louise" sort="Lafontaine, Anne Louise" uniqKey="Lafontaine A" first="Anne-Louise" last="Lafontaine">Anne-Louise Lafontaine</name><affiliation><nlm:aff id="awu251-AFF3">3 Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada</nlm:aff></affiliation></author><author><name sortKey="Rouleau, Guy A" sort="Rouleau, Guy A" uniqKey="Rouleau G" first="Guy A." last="Rouleau">Guy A. Rouleau</name><affiliation><nlm:aff id="awu251-AFF2">2 Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Québec, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="awu251-AFF3">3 Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada</nlm:aff></affiliation></author><author><name sortKey="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><affiliation><nlm:aff id="awu251-AFF1">1 Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal, Montréal, Québec, H3W 1W5, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="awu251-AFF5">5 Département de Radiologie, Université de Montréal, Montréal, Québec, Canada</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25212851</idno><idno type="pmc">4208466</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208466</idno><idno type="RBID">PMC:4208466</idno><idno type="doi">10.1093/brain/awu251</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000526</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000526</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Dopamine transporter <italic>SLC6A3</italic> genotype affects cortico-striatal activity of set-shifts in Parkinson’s disease</title><author><name sortKey="Habak, Claudine" sort="Habak, Claudine" uniqKey="Habak C" first="Claudine" last="Habak">Claudine Habak</name><affiliation><nlm:aff id="awu251-AFF1">1 Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal, Montréal, Québec, H3W 1W5, Canada</nlm:aff></affiliation></author><author><name sortKey="Noreau, Anne" sort="Noreau, Anne" uniqKey="Noreau A" first="Anne" last="Noreau">Anne Noreau</name><affiliation><nlm:aff id="awu251-AFF2">2 Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Québec, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="awu251-AFF3">3 Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada</nlm:aff></affiliation></author><author><name sortKey="Nagano Saito, Atsuko" sort="Nagano Saito, Atsuko" uniqKey="Nagano Saito A" first="Atsuko" last="Nagano-Saito">Atsuko Nagano-Saito</name><affiliation><nlm:aff id="awu251-AFF1">1 Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal, Montréal, Québec, H3W 1W5, Canada</nlm:aff></affiliation></author><author><name sortKey="Mejia Constain, Beatriz" sort="Mejia Constain, Beatriz" uniqKey="Mejia Constain B" first="Beatriz" last="Mejía-Constaín">Beatriz Mejía-Constaín</name><affiliation><nlm:aff id="awu251-AFF1">1 Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal, Montréal, Québec, H3W 1W5, Canada</nlm:aff></affiliation></author><author><name sortKey="Degroot, Clotilde" sort="Degroot, Clotilde" uniqKey="Degroot C" first="Clotilde" last="Degroot">Clotilde Degroot</name><affiliation><nlm:aff id="awu251-AFF1">1 Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal, Montréal, Québec, H3W 1W5, Canada</nlm:aff></affiliation></author><author><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><affiliation><nlm:aff id="awu251-AFF4">4 Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Chouinard, Sylvain" sort="Chouinard, Sylvain" uniqKey="Chouinard S" first="Sylvain" last="Chouinard">Sylvain Chouinard</name><affiliation><nlm:aff id="awu251-AFF2">2 Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Québec, Canada</nlm:aff></affiliation></author><author><name sortKey="Lafontaine, Anne Louise" sort="Lafontaine, Anne Louise" uniqKey="Lafontaine A" first="Anne-Louise" last="Lafontaine">Anne-Louise Lafontaine</name><affiliation><nlm:aff id="awu251-AFF3">3 Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada</nlm:aff></affiliation></author><author><name sortKey="Rouleau, Guy A" sort="Rouleau, Guy A" uniqKey="Rouleau G" first="Guy A." last="Rouleau">Guy A. Rouleau</name><affiliation><nlm:aff id="awu251-AFF2">2 Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Québec, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="awu251-AFF3">3 Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada</nlm:aff></affiliation></author><author><name sortKey="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><affiliation><nlm:aff id="awu251-AFF1">1 Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal, Montréal, Québec, H3W 1W5, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="awu251-AFF5">5 Département de Radiologie, Université de Montréal, Montréal, Québec, Canada</nlm:aff></affiliation></author></analytic><series><title level="j">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Parkinson’s disease is a neurodegenerative condition that affects motor function along with a wide range of cognitive domains, including executive function. The hallmark of the pathology is its significant loss of nigrostriatal dopamine, which is necessary for the cortico-striatal interactions that underlie executive control. Striatal dopamine reuptake is mediated by the <italic>SLC6A3</italic> gene (formerly named <italic>DAT1</italic>) and its polymorphisms, which have been largely overlooked in Parkinson’s disease. Thirty patients (ages 53–68 years; 19 males, 11 females) at early stages of Parkinson’s disease, were genotyped according to a 9-repeat (9R) or 10-repeat (10R) allele on the <italic>SLC6A3/DAT1</italic> gene. They underwent neuropsychological assessment and functional magnetic resonance imaging while performing a set-shifting task (a computerized Wisconsin Card Sorting Task) that relies on fronto-striatal interactions. Patients homozygous on the 10R allele performed significantly better on working memory tasks than 9R-carrier patients. Most importantly, patients carrying a 9R allele exhibited less activation than their 10R homozygous counterparts in the prefrontal cortex, premotor cortex and caudate nucleus, when planning and executing a set-shift. This pattern was exacerbated for conditions that usually recruit the striatum compared to those that do not. This is the first study indicating that the <italic>SLC6A3/DAT1</italic> genotype has a significant effect on fronto-striatal activation and performance in Parkinson’s disease. This effect is stronger for conditions that engage the striatum. Longitudinal studies are warranted to assess this polymorphism’s effect on the clinical evolution of patients with Parkinson’s disease, especially with cognitive decline.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Brain</journal-id><journal-id journal-id-type="iso-abbrev">Brain</journal-id><journal-id journal-id-type="publisher-id">brainj</journal-id><journal-id journal-id-type="hwp">brain</journal-id><journal-title-group><journal-title>Brain</journal-title></journal-title-group><issn pub-type="ppub">0006-8950</issn><issn pub-type="epub">1460-2156</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25212851</article-id><article-id pub-id-type="pmc">4208466</article-id><article-id pub-id-type="doi">10.1093/brain/awu251</article-id><article-id pub-id-type="publisher-id">awu251</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Articles</subject></subj-group></article-categories><title-group><article-title>Dopamine transporter <italic>SLC6A3</italic> genotype affects cortico-striatal activity of set-shifts in Parkinson’s disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Habak</surname><given-names>Claudine</given-names></name><xref ref-type="aff" rid="awu251-AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Noreau</surname><given-names>Anne</given-names></name><xref ref-type="aff" rid="awu251-AFF2"><sup>2</sup></xref><xref ref-type="aff" rid="awu251-AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nagano-Saito</surname><given-names>Atsuko</given-names></name><xref ref-type="aff" rid="awu251-AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mejía-Constaín</surname><given-names>Beatriz</given-names></name><xref ref-type="aff" rid="awu251-AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Degroot</surname><given-names>Clotilde</given-names></name><xref ref-type="aff" rid="awu251-AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Strafella</surname><given-names>Antonio P.</given-names></name><xref ref-type="aff" rid="awu251-AFF4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chouinard</surname><given-names>Sylvain</given-names></name><xref ref-type="aff" rid="awu251-AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lafontaine</surname><given-names>Anne-Louise</given-names></name><xref ref-type="aff" rid="awu251-AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rouleau</surname><given-names>Guy A.</given-names></name><xref ref-type="aff" rid="awu251-AFF2"><sup>2</sup></xref><xref ref-type="aff" rid="awu251-AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Monchi</surname><given-names>Oury</given-names></name><xref ref-type="aff" rid="awu251-AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="awu251-AFF5"><sup>5</sup></xref></contrib><aff id="awu251-AFF1">1 Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal, Montréal, Québec, H3W 1W5, Canada</aff><aff id="awu251-AFF2">2 Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Québec, Canada</aff><aff id="awu251-AFF3">3 Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada</aff><aff id="awu251-AFF4">4 Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada</aff><aff id="awu251-AFF5">5 Département de Radiologie, Université de Montréal, Montréal, Québec, Canada</aff></contrib-group><author-notes><corresp>Correspondence to: Dr Oury Monchi, Hotchkiss Brain Institute, Health Research Innovation Centre, Room 1AC64, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1 E-mail: <email>oury.monchi@umontreal.ca</email></corresp></author-notes><pub-date pub-type="ppub"><month>11</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>10</day><month>9</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>11</month><year>2015</year></pub-date><pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
<volume>137</volume><issue>11</issue><fpage>3025</fpage><lpage>3035</lpage><history><date date-type="received"><day>1</day><month>6</month><year>2014</year></date><date date-type="rev-recd"><day>9</day><month>7</month><year>2014</year></date><date date-type="accepted"><day>23</day><month>7</month><year>2014</year></date></history><permissions><copyright-statement>© The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com</copyright-statement><copyright-year>2014</copyright-year></permissions><abstract><p>Parkinson’s disease is a neurodegenerative condition that affects motor function along with a wide range of cognitive domains, including executive function. The hallmark of the pathology is its significant loss of nigrostriatal dopamine, which is necessary for the cortico-striatal interactions that underlie executive control. Striatal dopamine reuptake is mediated by the <italic>SLC6A3</italic> gene (formerly named <italic>DAT1</italic>) and its polymorphisms, which have been largely overlooked in Parkinson’s disease. Thirty patients (ages 53–68 years; 19 males, 11 females) at early stages of Parkinson’s disease, were genotyped according to a 9-repeat (9R) or 10-repeat (10R) allele on the <italic>SLC6A3/DAT1</italic> gene. They underwent neuropsychological assessment and functional magnetic resonance imaging while performing a set-shifting task (a computerized Wisconsin Card Sorting Task) that relies on fronto-striatal interactions. Patients homozygous on the 10R allele performed significantly better on working memory tasks than 9R-carrier patients. Most importantly, patients carrying a 9R allele exhibited less activation than their 10R homozygous counterparts in the prefrontal cortex, premotor cortex and caudate nucleus, when planning and executing a set-shift. This pattern was exacerbated for conditions that usually recruit the striatum compared to those that do not. This is the first study indicating that the <italic>SLC6A3/DAT1</italic> genotype has a significant effect on fronto-striatal activation and performance in Parkinson’s disease. This effect is stronger for conditions that engage the striatum. Longitudinal studies are warranted to assess this polymorphism’s effect on the clinical evolution of patients with Parkinson’s disease, especially with cognitive decline.</p></abstract><kwd-group kwd-group-type="keywords"><kwd>polymorphism</kwd><kwd><italic>SLC6A3/DAT1</italic></kwd><kwd>dopamine</kwd><kwd>executive function</kwd><kwd>functional MRI</kwd></kwd-group><counts><page-count count="11"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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