Browsing by Subject "Dopamine transporter"

Now showing 1 - 3 of 3
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    AZI23'UTR Is a New SLC6A3 Downregulator Associated with an Epistatic Protection Against Substance Use Disorders
    (Springer Nature, 2018-07) Liu, Kefu; Yu, Jinlong; Zhao, Juan; Zhou, Yanhong; Xiong, Nian; Xu, Jie; Wang, Tao; Bell, Richard L.; Qing, Hong; Lin, Zhicheng; Psychiatry, School of Medicine
    Regulated activity of SLC6A3, which encodes the human dopamine transporter (DAT), contributes to diseases such as substance abuse disorders (SUDs); however, the exact transcription mechanism remains poorly understood. Here, we used a common genetic variant of the gene, intron 1 DNP1B sequence, as bait to screen and clone a new transcriptional activity, AZI23'UTR, for SLC6A3. AZI23'UTR is a 3' untranslated region (3'UTR) of the human 5-Azacytidine Induced 2 gene (AZI2) but appeared to be transcribed independently of AZI2. Found to be present in both human cell nuclei and dopamine neurons, this RNA was shown to downregulate promoter activity through a variant-dependent mechanism in vitro. Both reduced RNA density ratio of AZI23'UTR/AZI2 and increased DAT mRNA levels were found in ethanol-naive alcohol-preferring rats. Secondary analysis of dbGaP GWAS datasets (Genome-Wide Association Studies based on the database of Genotypes and Phenotypes) revealed significant interactions between regions upstream of AZI23'UTR and SLC6A3 in SUDs. Jointly, our data suggest that AZI23'UTR confers variant-dependent transcriptional regulation of SLC6A3, a potential risk factor for SUDs.
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    The effects of DAT1 genotype on fMRI activation in an emotional go/no-go task
    (Springer, 2017-02) Brown, Brenna K.; Murrell, Jill; Karne, Harish; Anand, Amit; Pathology and Laboratory Medicine, School of Medicine
    Dopaminergic brain circuits participate in emotional processing and impulsivity. The dopamine transporter (DAT) modulates dopamine reuptake. A variable number tandem repeat (VNTR) in the dopamine transporter gene (DAT1) affects DAT expression. The influence of DAT1 genotype on neural activation during emotional processing and impulse inhibition has not been examined. Forty-two healthy subjects were classified as 9DAT (n = 17) or 10DAT (n = 25) based on DAT1 genotype (9DAT = 9R/9R and 9R/10R; 10DAT = 10R/10R). Subjects underwent fMRI during non-emotional and emotional go/no-go tasks. Subjects were instructed to inhibit responses to letters, happy faces, or sad faces in separate blocks. Accuracy and reaction time did not differ between groups. Within group results showed activation in regions previously implicated in emotional processing and response inhibition. Between groups results showed increased activation in 9DAT individuals during inhibition. During letter inhibition, 9DAT individuals exhibited greater activation in right inferior parietal regions. During sad inhibition, 9DAT Individuals exhibited greater activation in frontal, posterior cingulate, precuneus, right cerebellar, left paracentral, and right occipital brain regions. The interaction between DAT genotype and response type in sad versus letter stimuli showed increased activation in 9DAT individuals during sad no-go responses in the anterior cingulate cortex, extending into frontal-orbital regions. 9DAT individuals have greater activation than 10DAT individuals during neutral and sad inhibition, showing that genotypic variation influencing basal dopamine levels can alter the neural basis of emotional processing and response inhibition. This may indicate that 9R carriers exert more effort to overcome increased basal dopamine activation when inhibiting responses in emotional contexts.
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    Virtual reality cognitive intervention for heart failure: CORE study protocol
    (Alzheimer’s Association, 2022-03-15) Jung, Miyeon; Apostolova, Liana G.; Moser, Debra K.; Gradus-Pizlo, Irmina; Gao, Sujuan; Rogers, Jeff L.; Pressler, Susan J.; School of Nursing
    Introduction: Heart failure (HF) is a prevalent, serious chronic illness that affects 6.5 million adults in the United States. Among patients with HF, the prevalence of attention impairment is reported to range from 15% to 27%. Although attention is fundamental to human activities including HF self-care, cognitive interventions for patients with HF that target improvement in attention are scarce. The COgnitive intervention to Restore attention using nature Environment (CORE) study aims to test the preliminary efficacy of the newly developed Nature-VR, a virtual reality-based cognitive intervention that is based on the restorative effects of nature. Nature-VR development was guided by Attention Restoration Theory. The target outcomes are attention, HF self-care, and health-related quality of life (HRQoL). Our exploratory aims examine the associations between attention and several putative/established HF biomarkers (eg, oxygen saturation, brain-derived neurotrophic factor, apolipoprotein E, dopamine receptor, and dopamine transporter genes) as well as the effect of Nature-VR on cognitive performance in other domains (ie, global cognition, memory, visuospatial, executive function, and language), cardiac and neurological events, and mortality. Methods: This single-blinded, two-group randomized-controlled pilot study will enroll 74 participants with HF. The Nature-VR intervention group will view three-dimensional nature pictures using a virtual reality headset for 10 minutes per day, 5 days per week for 4 weeks (a total of 200 minutes). The active comparison group, Urban-VR, will view three-dimensional urban pictures using a virtual reality headset to match the Nature-VR intervention in intervention dose and delivery mode, but not in content. After baseline interviews, four follow-up interviews will be conducted to assess sustained effects of Nature-VR at 4, 8, 26, and 52 weeks. Discussion: The importance and novelty of this study consists of using a first-of-its kind, immersive virtual reality technology to target attention and in investigating the health outcomes of the Nature-VR cognitive intervention among patients with HF.