ParkinsonCanadaV1, Main, Exploration, bibRecord, 000A88

Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson’s disease

Identifieur interne : 000A88 ( Main/Exploration ); précédent : 000A87; suivant : 000A89

Dopamine 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 Mejía-Constaín [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.

RBID : PMC:4208466

English descriptors

KwdEn :
- Aged, Dopamine Plasma Membrane Transport Proteins (genetics), Dopamine Plasma Membrane Transport Proteins (physiology), Executive Function (physiology), Female, Frontal Lobe (physiopathology), Functional Neuroimaging, Heterozygote, Homozygote, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neostriatum (physiopathology), Parkinson Disease (genetics), Parkinson Disease (physiopathology), Polymorphism, Genetic.
MESH :
- chemical , genetics : Dopamine Plasma Membrane Transport Proteins.
- chemical , physiology : Dopamine Plasma Membrane Transport Proteins.
- genetics : Parkinson Disease.
- physiology : Executive Function.
- physiopathology : Frontal Lobe, Neostriatum, Parkinson Disease.
- Aged, Female, Functional Neuroimaging, Heterozygote, Homozygote, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Polymorphism, Genetic.

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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208466

DOI: 10.1093/brain/awu251
PubMed: 25212851
PubMed Central: 4208466

Affiliations:

Le document en format XML

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<term>Dopamine Plasma Membrane Transport Proteins (physiology)</term>
<term>Executive Function (physiology)</term>
<term>Female</term>
<term>Frontal Lobe (physiopathology)</term>
<term>Functional Neuroimaging</term>
<term>Heterozygote</term>
<term>Homozygote</term>
<term>Humans</term>
<term>Magnetic Resonance Imaging</term>
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<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>
<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="Mejía-Constaín">Beatriz Mejía-Constaín</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>

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La maladie de Parkinson au Canada (serveur d'exploration)

Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson’s disease

Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson’s disease

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	La maladie de Parkinson au Canada (serveur d'exploration)
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