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DAT transporter

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https://www.readbyqxmd.com/read/29348315/whole-body-biodistribution-and-dosimetry-of-the-dopamine-transporter-radioligand-18f-fe-pe2i-in-human-subjects
#1
Helena Lizana, Lennart Johansson, Jan E Axelsson, Anne Larsson Strömvall, Mattias Ögren, Jan Linder, Christer Halldin, Andrea Varrone, Susanna Jakobson Mo
18F-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4'-methyl-phenyl) nortropane (18F-FE-PE2I) was recently developed and has shown adequate affinity and high selectivity for the dopamine transporter (DAT). Previous studies have shown promising results for 18F-FE-PE2I as a suitable radioligand for DAT-imaging. In this study, we investigate the whole body biodistribution and dosimetry of 18F-FE-PE2I in healthy volunteers to support the utility of it as a suitable positron emission tomography (PET) imaging agent for the DAT...
January 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29348190/pronounced-hyperactivity-cognitive-dysfunctions-and-bdnf-dysregulation-in-dopamine-transporter-knockout-rats
#2
Damiana Leo, Ilya Sukhanov, Francesca Zoratto, Placido Illiano, Lucia Caffino, Fabrizio Sanna, Giulia Messa, Marco Emanuele, Alessandro Esposito, Maria Dorofeikova, Evgeny A Budygin, Liudmila Mus, Evgenia E Efimova, Marco Niello, Stefano Espinoza, Tatyana D Sotnikova, Marius C Hoener, Gianni Laviola, Fabio Fumagalli, Walter Adriani, Raul R Gainetdinov
Dopamine (DA) controls many vital physiological functions and is critically involved in several neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder (ADHD). The major function of the plasma membrane dopamine transporter (DAT) is the rapid uptake of released DA into presynaptic nerve terminals leading to control of both the extracellular levels of DA and the intracellular stores of DA. Here, we present a newly developed strain of rats (DAT-knockout, DAT-KO rats) in which the gene encoding the DAT has been disrupted by using zinc finger nuclease technology (ZFN)...
January 18, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29343767/blockade-of-trpv1-inhibits-methamphetamine-induced-rewarding-effects
#3
Yu-Hua Tian, Shi-Xun Ma, Kwang-Wook Lee, Sunmee Wee, George F Koob, Seok-Yong Lee, Choon-Gon Jang
Methamphetamine (MAP) is the most widely used psychostimulant in the world, but the exact mechanisms underlying MAP addiction are not yet fully understood. Recent studies have identified the distribution of TRPV1 in several brain regions that are related to drug addiction, including nucleus accumbens (NAc) and dorsal striatum (DSt). In the present study, we performed conditioned place preference (CPP) and self-administration tests to examine the effects of capsazepine (CPZ) and SB366791 (SB) on MAP reward. We found that both CPZ and SB significantly inhibited MAP-induced CPP and self-administration; in contrast, TRPV1 knock-out (KO) mice did not develop MAP-induced CPP...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329781/dopamine-transporter-trafficking-is-regulated-by-neutral-sphingomyelinase-2-ceramide-kinase
#4
Jong Hoon Won, Seok Kyun Kim, In Chul Shin, Hae Chan Ha, Ji Min Jang, Moon Jung Back, Dae Kyong Kim
Dopamine (DA) reuptake is the primary mechanism to terminate dopaminergic transmission in the synaptic cleft. The dopamine transporter (DAT) has an important role in the regulation of DA reuptake. This study provides anatomical and physiological evidence that DAT recycling is regulated by ceramide kinase via the sphingomyelin pathway. First, the results show that DAT and neutral sphingomyelinase 2 (nSMase2) were successfully co-precipitated from striatal samples and were colocalized in the mouse striatum or PC12 cells...
January 9, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29329285/a-direct-interaction-of-cholesterol-with-the-dopamine-transporter-prevents-its-out-to-inward-transition
#5
Talia Zeppelin, Lucy Kate Ladefoged, Steffen Sinning, Xavier Periole, Birgit Schiøtt
Monoamine transporters (MATs) carry out neurotransmitter reuptake from the synaptic cleft, a key step in neurotransmission, which is targeted in the treatment of neurological disorders. Cholesterol (CHOL), a major component of the synaptic plasma membrane, has been shown to exhibit a modulatory effect on MATs. Recent crystal structures of the dopamine transporter (DAT) revealed the presence of two conserved CHOL-like molecules, suggesting a functional protein-CHOL direct interaction. Here, we present extensive atomistic molecular dynamics (MD) simulations of DAT in an outward-facing conformation...
January 12, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29321352/genetic-analysis-of-55-northern-vietnamese-patients-with-wilson-disease-seven-novel-mutations-in-atp7b
#6
Le Anh Tuan Pham, Trong Tue Nguyen, Hoang Bich Nga Le, Dat Quoc Tran, Cam Tu Ho, Thinh Huy Tran, Van Thanh Ta, The Hung Bui, Van Khanh Tran
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The gene responsible for WD was discovered in 1993 and is located on chromosome 13 at 13q14.3. It encodes a copper-specific transporting P-type ATPase. Early diagnosis can improve treatment outcome and decrease the rate of disability or even mortality.We used Sanger sequencing to identify mutation hot spots in 55 northern Vietnamese with a clinical diagnosis of WD. Mutations were screened and detected by direct DNA sequencing. A total of 26 different ATP7B gene mutations were identified, including seven novel mutations (five nonsense and two missense mutations)...
December 2017: Journal of Genetics
https://www.readbyqxmd.com/read/29317605/non-invasive-modulation-reduces-repetitive-behavior-in-a-rat-model-through-the-sensorimotor-cortico-striatal-circuit
#7
Henriette Edemann-Callesen, Bettina Habelt, Franziska Wieske, Mark Jackson, Niranjan Khadka, Daniele Mattei, Nadine Bernhardt, Andreas Heinz, David Liebetanz, Marom Bikson, Frank Padberg, Ravit Hadar, Michael A Nitsche, Christine Winter
Involuntary movements as seen in repetitive disorders such as Tourette Syndrome (TS) results from cortical hyperexcitability that arise due to striato-thalamo-cortical circuit (STC) imbalance. Transcranial direct current stimulation (tDCS) is a stimulation procedure that changes cortical excitability, yet its relevance in repetitive disorders such as TS remains largely unexplored. Here, we employed the dopamine transporter-overexpressing (DAT-tg) rat model to investigate behavioral and neurobiological effects of frontal tDCS...
January 10, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29299388/individual-differences-in-eeg-correlates-of-recognition-memory-due-to-dat-polymorphisms
#8
Paolo Medrano, Erika Nyhus, Andrew Smolen, Tim Curran, Robert S Ross
Introduction: Although previous research suggests that genetic variation in dopaminergic genes may affect recognition memory, the role dopamine transporter expression may have on the behavioral and EEG correlates of recognition memory has not been well established. Objectives: The study aims to reveal how individual differences in dopaminergic functioning due to genetic variations in the dopamine transporter gene influences behavioral and EEG correlates of recognition memory...
December 2017: Brain and Behavior
https://www.readbyqxmd.com/read/29289701/dopamine-transporter-knockdown-mice-in-the-behavioral-pattern-monitor-a-robust-reproducible-model-for-mania-relevant-behaviors
#9
Molly A Kwiatkowski, Gerhard Hellemann, Catherine A Sugar, Zackary A Cope, Arpi Minassian, William Perry, Mark A Geyer, Jared W Young
Efforts to replicate results from both basic and clinical models have highlighted problems with reproducibility in science. In psychiatry, reproducibility issues are compounded because the complex behavioral syndromes make many disorders challenging to model. We develop translatable tasks that quantitatively measure psychiatry-relevant behaviors across species. The behavioral pattern monitor (BPM) was designed to analyze exploratory behaviors, which are altered in patients with bipolar disorder (BD), especially during mania episodes...
December 28, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29281965/is-dopamine-transporter-mediated-dopaminergic-signaling-in-the-retina-a-noninvasive-biomarker-for-attention-deficit-hyperactivity-disorder-a-study-in-a-novel-dopamine-transporter-variant-val559-transgenic-mouse-model
#10
Heng Dai, Chad R Jackson, Gwynne L Davis, Randy D Blakely, Douglas G McMahon
BACKGROUND: Dopamine (DA) is a critical neuromodulator in the retina. Disruption of retinal DA synthesis and signaling significantly attenuates light-adapted, electroretinogram (ERG) responses, as well as contrast sensitivity and acuity. As these measures can be detected noninvasively, they may provide opportunities to detect disease processes linked to perturbed DA signaling. Recently, we identified a rare, functional DA transporter (DAT, SLC6A3) coding substitution, Ala559Val, in subjects with attention-deficit/hyperactivity disorder (ADHD), demonstrating that DAT Val559 imparts anomalous DA efflux (ADE) with attendant physiological, pharmacological, and behavioral phenotypes...
December 28, 2017: Journal of Neurodevelopmental Disorders
https://www.readbyqxmd.com/read/29273699/false-positive-dopamine-transporter-imaging-due-to-therapeutic-dextroamphetamine-amphetamine
#11
Joseph Frankl, Sudeshna Bose, Phillip H Kuo
Dopamine transporter (DAT) single-photon emission computed tomography (SPECT) is an accurate adjunct to clinical evaluation for Parkinson's disease (PD) in cases where the diagnosis is difficult. Dopaminergic medications may significantly impact DAT availability and thus uptake of DAT tracers. A patient had a false-positive DAT-SPECT while on dextroamphetamine/amphetamine for attention deficit/hyperactivity disorder. DAT-SPECT normalized after withholding amphetamine therapy. This report demonstrates that an accurate medication history combined with the knowledge of drugs that interfere with DAT imaging is critical to ensure accuracy...
December 22, 2017: Journal of Nuclear Medicine Technology
https://www.readbyqxmd.com/read/29261228/overview-of-monoamine-transporters
#12
Shaili Aggarwal, Ole V Mortensen
The dopamine (DAT), serotonin (SERT), and norepinephrine (NET) transporters, which are collectively referred to as monoamine transporters (MATs), play significant roles in regulating the neuronal response to these neurotransmitters. MATs terminate the action of these neurotransmitters by translocating them from the synaptic space into the presynaptic neurons. These three transmitters are responsible for controlling a number of physiological, emotional, and behavioral functions, with their transporters being the site of action of drugs employed for the treatment of a variety of conditions, including depression, anxiety, ADHD, schizophrenia, and psychostimulant abuse...
December 20, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/29261226/in-vitro-assays-for-the-functional-characterization-of-the-dopamine-transporter-dat
#13
Shaili Aggarwal, Ole V Mortensen
Detailed in this unit are protocols for studying the in vitro uptake of dopamine (DA) as a means for defining the functional characteristics of dopamine transporters. All assays are performed using commercially available cell lines that transiently express the transporter under investigation. The three main assays provided are: a kinetic assay to calculate the affinity (KM ) and maximal velocity (Vmax ) of radiolabeled DA uptake into cells; concentration-response assays to measure the potencies (IC50 /Ki values) of test compounds as transport inhibitors; and an efflux assay to assess the ability and potency (EC50 ) of a ligand to elicit reverse transport of DA accumulated in the cell...
December 20, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/29258773/latch-and-trigger-role-for-r445-in-dat-transport-explains-molecular-basis-of-dtds
#14
Maarten E A Reith, Kymry T Jones, Juan Zhen, Sid Topiol
A recent study reports on five different mutations as sources of dopamine transporter (DAT) deficiency syndrome (DTDS). One of these mutations, R445C, is believed to be located on the intracellular side of DAT distal to the primary (S1) or secondary (S2) sites to which substrate binding is understood to occur. Thus, the molecular mechanism by which the R445C mutation results in DAT transport deficiency has eluded explanation. However, the recently reported X-ray structures of the endogenous amine transporters for dDAT and hSERT revealed the presence of a putative salt bridge between R445 and E428 suggesting a possible mechanism...
December 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29240240/ultrasound-triggered-effects-of-the-microbubbles-coupled-to-gdnf-and-nurr1-loaded-pegylated-liposomes-in-a-rat-model-of-parkinson-s-disease
#15
Peijian Yue, Lin Gao, Xuejing Wang, Xuebing Ding, Junfang Teng
The purpose of this study was to investigate ultrasound-triggered effects of the glial cell line-derived neurotrophic factor (GDNF) + nuclear receptor-related factor 1 (Nurr1)-polyethylene glycol (PEG)ylated liposomes-coupled microbubbles (PLs-GDNF+Nurr1-MBs) on behavioral impairment and neuron loss in a rat model of Parkinson's disease (PD). The unloaded PEGylated liposomes-coupled microbubbles (PLs-MBs) were characterized for zeta potential, particle size, and concentration. 6-hydroxydopamine (6-OHDA) was used to establish the PD rat model...
December 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29234141/cannabinoid-type-2-receptors-in-dopamine-neurons-inhibits-psychomotor-behaviors-alters-anxiety-depression-and-alcohol-preference
#16
Qing-Rong Liu, Ana Canseco-Alba, Hai-Ying Zhang, Patricia Tagliaferro, Monika Chung, Eugene Dennis, Branden Sanabria, Norman Schanz, Joao Carlos Escosteguy-Neto, Hiroki Ishiguro, Zhicheng Lin, Susan Sgro, Claire M Leonard, Jair Guilherme Santos-Junior, Eliot L Gardner, Josephine M Egan, Jeung Woon Lee, Zheng-Xiong Xi, Emmanuel S Onaivi
Cannabinoid CB2 receptors (CB2Rs) are expressed in mouse brain dopamine (DA) neurons and are involved in several DA-related disorders. However, the cell type-specific mechanisms are unclear since the CB2R gene knockout mice are constitutive gene knockout. Therefore, we generated Cnr2-floxed mice that were crossed with DAT-Cre mice, in which Cre- recombinase expression is under dopamine transporter gene (DAT) promoter control to ablate Cnr2 gene in midbrain DA neurons of DAT-Cnr2 conditional knockout (cKO) mice...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29230168/a-novel-dopamine-transporter-inhibitor-ce-123-improves-cognitive-flexibility-and-maintains-impulsivity-in-healthy-male-rats
#17
Agnieszka Nikiforuk, Predrag Kalaba, Marija Ilic, Volker Korz, Vladimir Dragačević, Judith Wackerlig, Thierry Langer, Harald Höger, Joanna Golebiowska, Piotr Popik, Gert Lubec
Reduced cognitive abilities are often characterized by an impairment of flexibility, i.e., the ability to switch from learned rules or categories that were important in certain contexts to different new modalities that rule the task. Drugs targeting the dopamine transporter (DAT) are widely used for their potential to enhance cognitive abilities. However, commercially available drugs are of limited specificity for DAT, blocking also noradrenaline and serotonine transporters, that can lead to unwanted side effects in healthy subjects...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29229294/impact-of-dha-intake-in-a-mouse-model-of-synucleinopathy
#18
Katherine Coulombe, Olivier Kerdiles, Cyntia Tremblay, Vincent Emond, Manon Lebel, Anne-Sophie Boulianne, Mélanie Plourde, Francesca Cicchetti, Frédéric Calon
Polyunsaturated fatty acids omega-3 (n-3 PUFA), such as docosahexaenoic acid (DHA), have been shown to prevent, and partially reverse, neurotoxin-induced nigrostriatal denervation in animal models of Parkinson's disease (PD). However, the accumulation of α-synuclein (αSyn) in cerebral tissues is equally important to the pathophysiology. To determine whether DHA intake improves various aspects related to synucleinopathy, ninety male mice overexpressing human αSyn under the Thy-1 promoter (Thy1-αSyn) were fed one of three diets (specially formulated control, low n-3 PUFA or high DHA) and compared to non-transgenic C57/BL6 littermate mice exposed to a control diet...
December 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29227643/structure-activity-relationship-studies-on-a-series-of-3%C3%AE-bis-4-fluorophenyl-methoxy-tropanes-and-3%C3%AE-bis-4-fluorophenyl-methylamino-tropanes-as-novel-atypical-dopamine-transporter-dat-inhibitors-for-the-treatment-of-cocaine-use-disorders
#19
Mu-Fa Zou, Jianjing Cao, Ara M Abramyan, Theresa Kopajtic, Claudio Zanettini, Daryl A Guthrie, Rana Rais, Barbara S Slusher, Lei Shi, Claus J Loland, Amy Hauck Newman
The development of medications to treat cocaine use disorders has thus far defied success, leaving this patient population without pharmacotherapeutic options. As the dopamine transporter (DAT) plays a prominent role in the reinforcing effects of cocaine that can lead to addiction, atypical DAT inhibitors have been developed that prevent cocaine from binding to DAT, but they themselves are not cocaine-like. Herein, a series of novel DAT inhibitors were synthesized, and based on its pharmacological profile, the lead compound 10a was evaluated in phase I metabolic stability studies in mouse liver microsomes and compared to cocaine in locomotor activity and drug discrimination paradigms in mice...
December 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29221813/neonatal-programming-with-testosterone-propionate-reduces-dopamine-transporter-expression-in-nucleus-accumbens-and-methylphenidate-induced-locomotor-activity-in-adult-female-rats
#20
Tatiana Dib, Jonathan Martínez-Pinto, Miguel Reyes-Parada, Gonzalo E Torres, Ramón Sotomayor-Zárate
Research in programming is focused on the study of stimuli that alters sensitive periods in development, such as prenatal and neonatal stages, that can produce long-term deleterious effects. These effects can occur in various organs or tissues such as the brain, affecting brain circuits and related behaviors. Our laboratory has demonstrated that neonatal programming with sex hormones affects the mesocorticolimbic circuitry, increasing the synthesis and release of dopamine (DA) in striatum and nucleus accumbens (NAcc)...
December 5, 2017: Behavioural Brain Research
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