Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson’s disease
Claudine Habak,Anne Noreau,Anne Noreau,Atsuko Nagano-Saito,Béatriz Mejia-Constain,Clotilde Degroot,Antonio P. Strafella,Sylvain Chouinard,Anne-Louise Lafontaine,Guy A. Rouleau,Guy A. Rouleau,Oury Monchi +11 more
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TLDR
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, and this effect is stronger for conditions that engage the striatum.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.read more
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Meta-Analysis of Parkinson's Disease and Alzheimer's Disease Revealed Commonly Impaired Pathways and Dysregulation of NRF2-Dependent Genes.
Qian Wang,Qian Wang,Wen-Xing Li,Wen-Xing Li,Shao-Xing Dai,Shao-Xing Dai,Yicheng Guo,Fei-Fei Han,Jun-Juan Zheng,Jun-Juan Zheng,Gong-Hua Li,Gong-Hua Li,Jing-Fei Huang +12 more
TL;DR: A meta-analysis with 9 microarray datasets of PD and AD studies found that MAFF was upregulated in all tissues and significantly negatively correlated with the 31 NRF2-dependent genes in diseased conditions, suggesting it might play an important role in dysfunction ofNRF2 regulatory network in PD.
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The Role of the SLC Transporters Protein in the Neurodegenerative Disorders.
Asli Ayka,Ahmet Özer Şehirli +1 more
TL;DR: The role of solute carrier transporters in neurodegenerative disorders such as Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, Parkinson’s diseases, depression, post-traumatic stress disorder, dementia, schizophrenia, and Epilepsy is reviewed and discussed to see how defects or absences in SLC transporter cause neurodegenersative disorders.
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The dopaminergic system dynamic in the time perception: a review of the evidence.
Victor Marinho,Thomaz Oliveira,Kaline Rocha,Jéssica Ribeiro,Francisco Magalhães,Thalys Bento,Giovanny R. Pinto,Bruna Velasques,Pedro Ribeiro,Luiza Medeiros Wanick Di Giorgio,Marco Orsini,Daya S. Gupta,Juliana Bittencourt,Victor Hugo Bastos,Silmar Teixeira +14 more
TL;DR: The dopaminergic system has great participation in impact on time perception and neurobiological basis of the executive functions and neurological diseases on the time perception is concluded.
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Markers of cognitive decline in PD: The case for heterogeneity
TL;DR: It is proposed that the current studies looking at different types of biomarkers provide support for different causes being associated with cognitive decline in PD, and large-scale multi-disciplinary and multi-modal longitudinal studies are required to identify the different phenotypes associated with different cognitive profiles and evolution in PD.
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Genetic Variation and Neuroplasticity: Role in Rehabilitation After Stroke.
TL;DR: Genetic polymorphisms for brain-derived neurotrophic factor, dopamine, and apolipoprotein E have been shown to impact neuroplasticity and motor learning and should be considered as possible predictors or covariates in studies that investigate neuroPlasticity, motor learning, or motor recovery after stroke.
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