Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson's disease
Identifieur interne : 000C04 ( Main/Exploration ); précédent : 000C03; suivant : 000C05Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson's disease
Auteurs : Claudine Habak [Canada] ; Anne Noreau [Canada] ; Atsuko Nagano-Saito [Canada] ; Beatriz Mejia-Constain [Canada] ; Clotilde Degroot [Canada] ; Antonio P. Strafella [Canada] ; Sylvain Chouinard [Canada] ; Anne-Louise Lafontaine [Canada] ; Guy A. Rouleau [Canada] ; Oury Monchi [Canada]Source :
- Brain [ 0006-8950 ] ; 2014.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
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 SLC6A3 gene (formerly named DAT1) 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 SLC6A3/DAT1 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 SLC6A3/ DAT1 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.
Affiliations:
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type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000024</idno><idno type="wicri:doubleKey">0006-8950:2014:Habak C:dopamine:transporter:slc</idno><idno type="wicri:Area/Main/Merge">000C09</idno><idno type="wicri:Area/Main/Curation">000C04</idno><idno type="wicri:Area/Main/Exploration">000C04</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Dopamine transporter SLC6A3 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 wicri:level="1"><inist:fA14 i1="01"><s1>Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal</s1><s2>Montréal, Quebec, H3W 1W5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montréal, Quebec, H3W 1W5</wicri:noRegion></affiliation></author><author><name sortKey="Noreau, Anne" sort="Noreau, Anne" uniqKey="Noreau A" first="Anne" last="Noreau">Anne Noreau</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)</s1><s2>Montreal, Québec</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Neurology and Neurosurgery, McGill University</s1><s2>Montréal, QC H3A 2B4</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></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 wicri:level="1"><inist:fA14 i1="01"><s1>Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal</s1><s2>Montréal, Quebec, H3W 1W5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montréal, Quebec, H3W 1W5</wicri:noRegion></affiliation></author><author><name sortKey="Mejia Constain, Beatriz" sort="Mejia Constain, Beatriz" uniqKey="Mejia Constain B" first="Beatriz" last="Mejia-Constain">Beatriz Mejia-Constain</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal</s1><s2>Montréal, Quebec, H3W 1W5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montréal, Quebec, H3W 1W5</wicri:noRegion></affiliation></author><author><name sortKey="Degroot, Clotilde" sort="Degroot, Clotilde" uniqKey="Degroot C" first="Clotilde" last="Degroot">Clotilde Degroot</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal</s1><s2>Montréal, Quebec, H3W 1W5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montréal, Quebec, H3W 1W5</wicri:noRegion></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 wicri:level="4"><inist:fA14 i1="04"><s1>Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Chouinard, Sylvain" sort="Chouinard, Sylvain" uniqKey="Chouinard S" first="Sylvain" last="Chouinard">Sylvain Chouinard</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)</s1><s2>Montreal, Québec</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)</wicri:noRegion></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 wicri:level="4"><inist:fA14 i1="03"><s1>Department of Neurology and Neurosurgery, McGill University</s1><s2>Montréal, QC H3A 2B4</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></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 wicri:level="1"><inist:fA14 i1="02"><s1>Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)</s1><s2>Montreal, Québec</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Neurology and Neurosurgery, McGill University</s1><s2>Montréal, QC H3A 2B4</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></affiliation></author><author><name sortKey="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Research Centre, Institut universitaire de Gériatrie de Montréal, University of Montréal</s1><s2>Montréal, Quebec, H3W 1W5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montréal, Quebec, H3W 1W5</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Département de Radiologie, Université de Montréal</s1><s2>Montréal, Québec</s2><s3>CAN</s3><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montréal, Québec</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Brain</title><title level="j" type="abbreviated">Brain</title><idno type="ISSN">0006-8950</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Brain</title><title level="j" type="abbreviated">Brain</title><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dopamine</term><term>Executive function</term><term>Genotype</term><term>Nervous system diseases</term><term>Nuclear magnetic resonance imaging</term><term>Parkinson disease</term><term>Polymorphism</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term><term>Dopamine</term><term>Génotype</term><term>Polymorphisme</term><term>Fonction exécutive</term><term>Imagerie RMN</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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 SLC6A3 gene (formerly named DAT1) 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 SLC6A3/DAT1 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 SLC6A3/ DAT1 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.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li><li>Québec</li></region><settlement><li>Montréal</li><li>Toronto</li></settlement><orgName><li>Université McGill</li><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Habak, Claudine" sort="Habak, Claudine" uniqKey="Habak C" first="Claudine" last="Habak">Claudine Habak</name></noRegion><name sortKey="Chouinard, Sylvain" sort="Chouinard, Sylvain" uniqKey="Chouinard S" first="Sylvain" last="Chouinard">Sylvain Chouinard</name><name sortKey="Degroot, Clotilde" sort="Degroot, Clotilde" uniqKey="Degroot C" first="Clotilde" last="Degroot">Clotilde Degroot</name><name sortKey="Lafontaine, Anne Louise" sort="Lafontaine, Anne Louise" uniqKey="Lafontaine A" first="Anne-Louise" last="Lafontaine">Anne-Louise Lafontaine</name><name sortKey="Mejia Constain, Beatriz" sort="Mejia Constain, Beatriz" uniqKey="Mejia Constain B" first="Beatriz" last="Mejia-Constain">Beatriz Mejia-Constain</name><name sortKey="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><name sortKey="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><name sortKey="Nagano Saito, Atsuko" sort="Nagano Saito, Atsuko" uniqKey="Nagano Saito A" first="Atsuko" last="Nagano-Saito">Atsuko Nagano-Saito</name><name sortKey="Noreau, Anne" sort="Noreau, Anne" uniqKey="Noreau A" first="Anne" last="Noreau">Anne Noreau</name><name sortKey="Noreau, Anne" sort="Noreau, Anne" uniqKey="Noreau A" first="Anne" last="Noreau">Anne Noreau</name><name sortKey="Rouleau, Guy A" sort="Rouleau, Guy A" uniqKey="Rouleau G" first="Guy A." last="Rouleau">Guy A. Rouleau</name><name sortKey="Rouleau, Guy A" sort="Rouleau, Guy A" uniqKey="Rouleau G" first="Guy A." last="Rouleau">Guy A. Rouleau</name><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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