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DAT transporter

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https://www.readbyqxmd.com/read/27913309/sequence-determinants-of-the-caenhorhabditis-elegansdopamine-transporter-dictating-in-vivoaxonal-export-and-synaptic-localization
#1
Sarah B Robinson, J Andrew Hardaway, Shannon L Hardie, Jane Wright, Ryan M Glynn, Daniel P Bermingham, Qiao Han, Sarah M Sturgeon, Phyllis Freeman, Randy D Blakely
The monoamine neurotransmitter dopamine (DA) acts across phylogeny to modulate both simple and complex behaviors. The presynaptic DA transporter (DAT) is a major determinant of DA signaling capacity in ensuring efficient extracellular DA clearance. In humans, DAT is also a major target for prescribed and abused psychostimulants. Multiple structural determinants of DAT function and regulation have been defined, though largely these findings have arisen from heterologous expression or ex vivo cell culture studies...
November 29, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27909828/the-dopamine-related-polymorphisms-bdnf-comt-drd2-drd3-and-drd4-are-not-linked-with-changes-in-csf-dopamine-levels-and-frequency-of-hiv-infection
#2
Anne Horn, C Scheller, S du Plessis, R Burger, G Arendt, J Joska, S Sopper, C M Maschke, M Obermann, I W Husstedt, J Hain, P Riederer, E Koutsilieri
We showed previously that higher levels in CSF dopamine in HIV patients are associated with the presence of the dopamine transporter (DAT) 10/10-repeat allele which was also detected more frequently in HIV-infected individuals compared to uninfected subjects. In the current study, we investigated further whether other genetic dopamine (DA)-related polymorphisms may be related with changes in CSF DA levels and frequency of HIV infection in HIV-infected subjects. Specifically, we studied genetic polymorphisms of brain-derived neurotrophic factor, catechol-O-methyltransferase, and dopamine receptors DRD2, DRD3, and DRD4 genetic polymorphisms in uninfected and HIV-infected people in two different ethnical groups, a German cohort (Caucasian, 72 individuals with HIV infection and 22 individuals without HIV infection) and a South African cohort (Xhosan, 54 individuals with HIV infection and 19 individuals without HIV infection)...
December 1, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27893588/suite-pet-ct-neuroimaging-for-the-diagnosis-of-parkinson-s-disease-statistical-parametric-mapping-analysis
#3
Ruimin Wang, Baixuan Xu, Zhe Guo, Tong Chen, Jinming Zhang, Yingmao Chen, Haiyan Zhu
OBJECTIVES: The aim of this study was to investigate the topographical distribution of dopamine transporter (DAT), dopamine D2 receptor, and glucose metabolism in Parkinson's disease (PD) using PET/computed tomography (CT) scanning and statistical parametric mapping (SPM) analysis. PARTICIPANTS AND METHODS: Seventy-four patients (58 PD patients and 16 normal controls) underwent DAT, D2 receptor, and glucose brain PET/CT scans using C-methyl-N-2-β-carbomethoxy-3-β-(4-fluorophenyl) tropane (C-β-CFT), C-raclopride (C-RAC), and fluorine-18-fluorodeoxyglucose (F-FDG) radiotracers for the respective scans...
November 28, 2016: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/27890676/combined-in-vitro-and-in-silico-approaches-to-the-assessment-of-stimulant-properties-of-novel-psychoactive-substances-the-case-of-the-benzofuran-5-mapb
#4
Michelle A Sahai, Colin Davidson, George Khelashvili, Vincenzo Barrese, Neelakshi Dutta, Harel Weinstein, Jolanta Opacka-Juffry
Novel psychoactive substances (NPS) are increasingly prevalent world-wide although their pharmacological characteristics are largely unknown; those with stimulant properties, due to interactions with the dopamine transporter (DAT), have addictive potential which their users may not realise. We evaluated the binding of 1-(1-benzofuran-5-yl)-N-methylpropan-2-amine (5-MAPB) to rat striatal DAT by means of quantitative autoradiography with [(125)I]RTI-121, and the effects of 5-MAPB on electrically-evoked dopamine efflux by fast-cyclic voltammetry in rat brain slices...
November 24, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/27883923/gilles-de-la-tourette-syndrome-is-associated-with-hypermethylation-of-the-dopamine-d2-receptor-gene
#5
Kirsten R Müller-Vahl, Gesa Loeber, Alexandra Kotsiari, Linda Müller-Engling, Helge Frieling
Several lines of evidence support a "dopaminergic hypothesis" in the pathophysiology of Gilles de la Tourette syndrome (TS). The aim of this study was to investigate for the first time epigenetic changes in DNA methylation in different dopamine genes in adult patients with TS. We included 51 well characterized adult patients with TS (41 males, 10 females, mean age = 35 ± 12.6 years, range, 18-71 years) and compared results with data from a group of 51 sex- and age-matched healthy controls. Bisulfite sequencing was used to measure peripheral DNA methylation of the dopamine transporter (DAT), the dopamine D2 receptor (DRD2), and the catechol-O-methyltransferase (COMT) genes...
November 12, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27879654/early-antipsychotic-treatment-in-juvenile-rats-elicits-long-term-alterations-to-the-dopamine-neurotransmitter-system
#6
Michael De Santis, Jiamei Lian, Xu-Feng Huang, Chao Deng
Prescription of antipsychotic drugs (APDs) to children has substantially increased in recent years. Whilst current investigations into potential long-term effects have uncovered some alterations to adult behaviours, further investigations into potential changes to neurotransmitter systems are required. The current study investigated potential long-term changes to the adult dopamine (DA) system following aripiprazole, olanzapine and risperidone treatment in female and male juvenile rats. Levels of tyrosine hydroxylase (TH), phosphorylated-TH (p-TH), dopamine active transporter (DAT), and D₁ and D₂ receptors were measured via Western blot and/or receptor autoradiography...
November 22, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27871051/aging-modifies-the-effect-of-gch1-rs11158026-on-dat-uptake-and-parkinson-s-disease-clinical-severity
#7
Joseph Webb, Auriel A Willette
Novel single nucleotide polymorphisms within Parkinson's disease (PD) can predict disease risk, but their influence on clinical, cognitive, and neurobiological indices remains unexplored. We investigated differences between functional polymorphisms at RS11158026 coding for guanosine triphosphate cyclohydrolase-1 (GCH1), an essential enzyme for dopamine production in nigrostriatal cells. Among newly diagnosed, untreated PD subjects and age-matched controls from the Parkinson's Progression Markers Initiative, T allele carriers showed higher PD risk (odds ratio = 1...
October 13, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27866858/clinical-variables-and-biomarkers-in-prediction-of-cognitive-impairment-in-patients-with-newly-diagnosed-parkinson-s-disease-a-cohort-study
#8
Anette Schrag, Uzma Faisal Siddiqui, Zacharias Anastasiou, Daniel Weintraub, Jonathan M Schott
BACKGROUND: Parkinson's disease is associated with an increased incidence of cognitive impairment and dementia. Predicting who is at risk of cognitive decline early in the disease course has implications for clinical prognosis and for stratification of participants in clinical trials. We assessed the use of clinical information and biomarkers as predictive factors for cognitive decline in patients with newly diagnosed Parkinson's disease. METHODS: The Parkinson's Progression Markers Initiative (PPMI) study is a cohort study in patients with newly diagnosed Parkinson's disease...
November 17, 2016: Lancet Neurology
https://www.readbyqxmd.com/read/27860344/combined-simulation-and-mutation-studies-to-elucidate-selectivity-of-unsubstituted-amphetamine-like-cathinones-at-the-dopamine-transporter
#9
Amir Seddik, Daan P Geerke, Thomas Stockner, Marion Holy, Oliver Kudlacek, Nicholas V Cozzi, Arnold E Ruoho, Harald H Sitte, Gerhard F Ecker
The dopamine and serotonin transporter proteins (DAT, SERT) play a vital role in behavior and mental illness. Although their substrate transport has been studied extensively, the molecular basis of their selectivity is not completely understood yet. In this study, we exploit molecular dynamics simulations combined with mutagenesis studies to shed light on the driving factors for DAT-over-SERT selectivity of a set of cathinones. Results indicate that these compounds can adopt two binding modes of which one is more favorable...
November 8, 2016: Molecular Informatics
https://www.readbyqxmd.com/read/27856628/analysis-of-extrastriatal-123i-fp-cit-binding-contributes-to-the-differential-diagnosis-of-parkinsonian-diseases
#10
Merijn Joling, Chris Vriend, Odile A Van den Heuvel, Pieter G H M Raijmakers, Paul A Jones, Henk W Berendse, Jan Booij
: (123)I-FP-CIT SPECT can visualise and quantify striatal dopamine transporter (DAT) binding in vivo. In addition, (123)I-FP-CIT has modest affinity for the serotonin transporter (SERT), predominantly represented in extrastriatal binding. Based on previous imaging studies that have suggested more pronounced degeneration of other monoaminergic systems in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) than in Parkinson's disease (PD), we hypothesised that, in addition to striatal DAT binding, there would be differences in extrastriatal (123)I-FP-CIT SPECT binding to SERT between MSA, PSP and PD...
November 17, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27836487/phosphorylation-mechanisms-in-dopamine-transporter-regulation
#11
REVIEW
James D Foster, Roxanne A Vaughan
The dopamine transporter (DAT) is a plasma membrane phosphoprotein that actively translocates extracellular dopamine (DA) into presynaptic neurons. The transporter is the primary mechanism for control of DA levels and subsequent neurotransmission, and is the target for abused and therapeutic drugs that exert their effects by suppressing reuptake. The transport capacity of DAT is acutely regulated by signaling systems and drug exposure, providing neurons the ability to fine-tune DA clearance in response to specific conditions...
November 8, 2016: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/27830575/neuropharmacology-of-3-4-methylenedioxypyrovalerone-mdpv-its-metabolites-and-related-analogs
#12
Michael H Baumann, Mohammad O Bukhari, Kurt R Lehner, Sebastien Anizan, Kenner C Rice, Marta Concheiro, Marilyn A Huestis
3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive component of so-called bath salts products that has caused serious medical consequences in humans. In this chapter, we review the neuropharmacology of MDPV and related analogs, and supplement the discussion with new results from our preclinical experiments. MDPV acts as a potent uptake inhibitor at plasma membrane transporters for dopamine (DAT) and norepinephrine (NET) in nervous tissue. The MDPV formulation in bath salts is a racemic mixture, and the S isomer is much more potent than the R isomer at blocking DAT and producing abuse-related effects...
November 10, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27814458/test-retest-reproducibility-of-extrastriatal-binding-with-123-i-fp-cit-spect-in-healthy-male-subjects
#13
Kiwamu Matsuoka, Fumihiko Yasuno, Takayuki Shinkai, Toshiteru Miyasaka, Masato Takahashi, Kuniaki Kiuchi, Jun Kosaka, Makoto Inoue, Kimihiko Kichikawa, Masatoshi Hasegawa, Toshifumi Kishimoto
(123)I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT) is used to assess striatal dopamine transporter (DAT) expression, but it can also quantify extrastriatal serotonin transporter (SERT) expressions. While FP-CIT uptake in extrastriatal regions has been quantified, no information exists on the reproducibility of the (123)I-FP-CIT specific uptake ratio (SUR) in extrastriatal regions. We investigated test-retest reproducibility of (123)I-FP-CIT binding in the striatum, the midbrain, and cortical regions in eight healthy male subjects...
December 30, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27791160/optogenetic-activation-of-dopamine-neurons-in-the-ventral-tegmental-area-induces-reanimation-from-general-anesthesia
#14
Norman E Taylor, Christa J Van Dort, Jonathan D Kenny, JunZhu Pei, Jennifer A Guidera, Ksenia Y Vlasov, Justin T Lee, Edward S Boyden, Emery N Brown, Ken Solt
Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine and methylphenidate are effective for increasing arousal and inducing reanimation, or active emergence from general anesthesia. DA neurons in the ventral tegmental area (VTA) are involved in reward processing, motivation, emotion, reinforcement, and cognition, but their role in regulating wakefulness is less clear. The current study was performed to test the hypothesis that selective optogenetic activation of VTA DA neurons is sufficient to induce arousal from an unconscious, anesthetized state...
October 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27789280/regional-influence-of-cocaine-on-evoked-dopamine-release-in-the-nucleus-accumbens-core-a-role-for-the-caudal-brainstem
#15
Ashlynn I Gerth, Amber L Alhadeff, Harvey J Grill, Mitchell F Roitman
Cocaine increases dopamine concentration in the nucleus accumbens through competitive binding to the dopamine transporter (DAT). However, it also increases the frequency of dopamine release events, a finding that cannot be explained by action at the DAT alone. Rather, this effect may be mediated by cocaine-induced modulation of brain regions that project to dopamine neurons. To explore regional contributions of cocaine to dopamine signaling, we administered cocaine to the lateral or fourth ventricles and compared the effects on dopamine release in the nucleus accumbens evoked by electrical stimulation of the ventral tegmental area to that of systemically-delivered cocaine...
October 24, 2016: Brain Research
https://www.readbyqxmd.com/read/27775946/comparison-of-dopamine-transporter-spect-and-123i-mibg-myocardial-scintigraphy-to-assess-clinical-severity-in-patients-with-parkinson-disease
#16
Nanami Okano, Mamoru Niitsu, Junji Tanaka, Takahiro Sasaki, Kazushi Takahashi, Nobuo Araki, Toshimasa Yamamoto, Shintaro Nakano, Shigeyuki Nishimura, Takaaki Senbonmatsu, Ichiro Matsunari
PURPOSE: The aim of our study was to evaluate the use of dopamine transporter (DAT) SPECT and I-MIBG myocardial scintigraphy to determine the clinical severity of Parkinson disease (PD), with a focus on motor impairments affecting activities of daily living (ADLs). METHODS: Data for 65 consecutive PD patients who underwent both DAT and MIBG imaging were reviewed. Associations between imaging variables and Hoehn and Yahr (H&Y) staging or self-supportive care ratings were investigated...
October 21, 2016: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/27771535/protective-effects-of-a-herbal-extract-combination-of-bupleurum-falcatum-paeonia-suffruticosa-and-angelica-dahurica-against-mptp-induced-neurotoxicity-via-regulation-of-nuclear-receptor-related-1-protein
#17
Yeomoon Sim, Gunhyuk Park, Hyeyoon Eo, Eugene Huh, Pil Sung Gu, Seon-Pyo Hong, Youngmi Kim Pak, Myung Sook Oh
Parkinson's disease (PD) is one of the progressive neurodegenerative diseases of whose condition is characterized by dopaminergic neuronal cell loss and dysfunction in the substantia nigra pars compacta (SNpc) and the striatum. Recent studies have demonstrated that the nuclear receptor-related 1 protein (Nurr1) is critical of dopaminergic phenotype induction in mesencephalic dopaminergic neurons. Further, Nurr1 engages in synthesizing and storing dopamine through regulating levels of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2)...
October 19, 2016: Neuroscience
https://www.readbyqxmd.com/read/27733628/modafinil-activates-phasic-dopamine-signaling-in-dorsal-and-ventral-striata
#18
Martin J Bobak, Matthew W Weber, Melissa A Doellman, Douglas R Schuweiler, Jeana M Athens, Steven A Juliano, Paul A Garris
Modafinil (MOD) exhibits therapeutic efficacy for treating sleep and psychiatric disorders, but its mechanism is incompletely understood. Compared to other psychostimulants inhibiting dopamine (DA) uptake, MOD weakly interacts with the dopamine transporter (DAT) and modestly elevates striatal dialysate DA, suggesting additional targets besides DAT. However, the ability of MOD to induce wakefulness is abolished with DAT knockout, conversely suggesting that DAT is necessary for MOD action. Another psychostimulant target, but one not established for MOD, is activation of phasic DA signaling...
October 12, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27732870/the-effects-of-reduced-dopamine-transporter-function-and-chronic-lithium-on-motivation-probabilistic-learning-and-neurochemistry-in-mice-modeling-bipolar-mania
#19
Morgane Milienne-Petiot, James P Kesby, Mary Graves, Jordy van Enkhuizen, Svetlana Semenova, Arpi Minassian, Athina Markou, Mark A Geyer, Jared W Young
BACKGROUND: Bipolar disorder (BD) mania patients exhibit poor cognition and reward-seeking/hypermotivation, negatively impacting a patient's quality of life. Current treatments (e.g., lithium), do not treat such deficits. Treatment development has been limited due to a poor understanding of the neural mechanisms underlying these behaviors. Here, we investigated putative mechanisms underlying cognition and reward-seeking/motivational changes relevant to BD mania patients using two validated mouse models and neurochemical analyses...
October 11, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27725851/bmp2-promotes-the-differentiation-of-neural-stem-cells-into-dopaminergic-neurons-in-vitro-via-mir-145-mediated-upregulation-of-nurr1-expression
#20
Wang Yan, Zhao-Ying Chen, Jia-Qi Chen, Hui-Min Chen
BACKGROUND: Neural stem cells (NSCs) are pluripotent and self-renewing cells which could differentiate into diverse types of neural cells, such as dopaminergic (DA) neurons, the loss of which is the typical characteristic of Parkinson's disease (PD). This study aimed to examine the molecular mechanisms of BMP2-mediating NSCs differentiation into DA neurons. METHODS: Different concentrations of BMP2 were used to induce the differentiation of NSCs into DA neurons, which were characterized by the number and the neurite lengths of tyrosine hydroxylase (TH)+ and dopamine transporter (DAT)+ neurons by immunocytochemistry...
2016: American Journal of Translational Research
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