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DAT transporter

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https://www.readbyqxmd.com/read/28106567/fractional-anisotropy-and-mean-diffusion-as-measures-of-dopaminergic-function-in-parkinson-s-disease-challenging-results
#1
Niklas Lenfeldt, Johan Eriksson, Björn Åström, Lars Forsgren, Susanna Jakobson
BACKGROUND: Diffusion tensor imaging (DTI) has been purported as an imaging technique to assess dopaminergic degeneration in Parkinson's disease. OBJECTIVE: To test if fractional anisotropy (FA) and mean diffusion (MD) in the basal ganglia as measured by DTI correlates with dopaminergic function as measured by dopamine transporter (DAT) and dopamine D2-receptor (D2R) SPECT. METHODS: One-hundred and eleven patients with Parkinson's disease (71±10 years) and thirty-one controls (68±7 years) performed DTI, DAT and D2R SPECT at baseline and four follow-ups (1-year: 89 patients/zero controls; 3-year: 72/11; 5-year: 48/17; and 8-year: 13/13)...
January 17, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28096460/occupancy-of-the-zinc-binding-site-by-transition-metals-decreases-the-substrate-affinity-of-the-human-dopamine-transporter-by-an-allosteric-mechanism
#2
Yang Li, Felix P Mayer, Peter S Hasenhuetl, Verena Burtscher, Klaus Schicker, Harald H Sitte, Michael Freissmuth, Walter Sandtner
The human dopamine transporter (DAT) has a tetrahedral Zn(2+)-binding site. Zn(2+)-binding sites are also recognized by other first row transition metals. Excessive accumulation of manganese or of copper can lead to Parkinsonism due to dopamine deficiency. Accordingly, we examined the effect of Mn(2+), Co(2+), Ni(2+) and Cu(2+)on transport-associated currents through DAT and DAT-H193K, a mutant with a disrupted Zn(2+)-binding site. All transition metals - but Mn(2+) - modulated the transport cycle of wild type DAT with affinities in the low µM range...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28094812/putative-presynaptic-dopamine-dysregulation-in-schizophrenia-is-supported-by-molecular-evidence-from-post-mortem-human-midbrain
#3
T D Purves-Tyson, S J Owens, D A Rothmond, G M Halliday, K L Double, J Stevens, T McCrossin, C Shannon Weickert
The dopamine hypothesis of schizophrenia posits that increased subcortical dopamine underpins psychosis. In vivo imaging studies indicate an increased presynaptic dopamine synthesis capacity in striatal terminals and cell bodies in the midbrain in schizophrenia; however, measures of the dopamine-synthesising enzyme, tyrosine hydroxylase (TH), have not identified consistent changes. We hypothesise that dopamine dysregulation in schizophrenia could result from changes in expression of dopamine synthesis enzymes, receptors, transporters or catabolic enzymes...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28093210/neuroprotection-by-paeoniflorin-in-the-mptp-mouse-model-of-parkinson-s-disease
#4
Meizhu Zheng, Chunming Liu, Yajun Fan, Pan Yan, Dongfang Shi, Yuchi Zhang
Paeoniflorin (PF) is a major bioactive ingredient in Radix Paeonia alba roots that has low toxicity and has been shown to have neuroprotective effects. Our in vitro experiments suggested that PF affords a significant neuroprotective effect against MPP(+)-induced damage and apoptosis in PC12 cells through Bcl-2/Bax/caspase-3 pathway. The objectives of the present study were to explore the potential neuroprotective effect of PF in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD)...
January 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28075498/tamoxifen-and-its-active-metabolites-inhibit-dopamine-transporter-function-independently-of-the-estrogen-receptors
#5
Sarah R Mikelman, Bipasha Guptaroy, Margaret Gnegy
As one of the primary mechanisms by which dopamine signaling is regulated, the dopamine transporter (DAT) is an attractive pharmacological target for the treatment of diseases based in dopaminergic dysfunction. In this work we demonstrate for the first time that the commonly prescribed breast cancer therapeutic tamoxifen and its major metabolites, 4-hydroxytamoxifen and endoxifen, inhibit DAT function. Tamoxifen inhibits [(3) H]dopamine uptake into hDAT-N2A cells via an uncompetitive or mixed mechanism. Endoxifen, an active metabolite of tamoxifen, asymmetrically inhibits DAT function in hDAT-N2A cells, showing a preference for the inhibition of amphetamine-stimulated dopamine efflux as compared to dopamine uptake...
January 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28072417/dopaminergic-dynamics-underlying-sex-specific-cocaine-reward
#6
Erin S Calipari, Barbara Juarez, Carole Morel, Deena M Walker, Michael E Cahill, Efrain Ribeiro, Ciorana Roman-Ortiz, Charu Ramakrishnan, Karl Deisseroth, Ming-Hu Han, Eric J Nestler
Although both males and females become addicted to cocaine, females transition to addiction faster and experience greater difficulties remaining abstinent. We demonstrate an oestrous cycle-dependent mechanism controlling increased cocaine reward in females. During oestrus, ventral tegmental area (VTA) dopamine neuron activity is enhanced and drives post translational modifications at the dopamine transporter (DAT) to increase the ability of cocaine to inhibit its function, an effect mediated by estradiol. Female mice conditioned to associate cocaine with contextual cues during oestrus have enhanced mesolimbic responses to these cues in the absence of drug...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28062370/treadmill-exercise-alleviates-motor-deficits-and-improves-mitochondrial-import-machinery-in-an-mptp-induced-mouse-model-of-parkinson-s-disease
#7
Jung-Hoon Koo, Joon-Yong Cho, Ung-Bae Lee
Alpha-synuclein (α-Syn) accumulation is significantly correlated with motor deficits and mitochondrial dysfunction in Parkinson's disease (PD), but the molecular mechanism underlying its pathogenesis is unclear. In this study, we investigated the effects of treadmill exercise on motor deficits and mitochondrial dysfunction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Treadmill exercise inhibited dopaminergic neuron loss by promoting the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) and seemed to improve cell survival by reducing α-Syn expression...
January 4, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28059145/a-markov-state-based-quantitative-kinetic-model-of-sodium-release-from-the-dopamine-transporter
#8
Asghar M Razavi, George Khelashvili, Harel Weinstein
The dopamine transporter (DAT) belongs to the neurotransmitter:sodium symporter (NSS) family of membrane proteins that are responsible for reuptake of neurotransmitters from the synaptic cleft to terminate a neuronal signal and enable subsequent neurotransmitter release from the presynaptic neuron. The release of one sodium ion from the crystallographically determined sodium binding site Na2 had been identified as an initial step in the transport cycle which prepares the transporter for substrate translocation by stabilizing an inward-open conformation...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28055236/characterization-of-vntrs-within-the-entire-region-of-slc6a3-and-its-association-with-hypertension
#9
Won-Tae Kim, Se-Ra Lee, Yun-Gil Roh, Seung Il Kim, Yung Hyun Choi, Mi-Hye Mun, Mi-So Jeong, Sang Seok Koh, Sun-Hee Leem
The dopamine transporter SLC6A3 (DAT1) mediates uptake of dopamine into presynaptic terminals. In addition, in previous reports, hypertensive rats were associated with DAT gene, but the genetic association with SLC6A3 and hypertension is still unknown. We examined the distribution of variable number of tandem repeats (VNTRs) and conducted polymorphic analysis of the entire region of SLC6A3. Ten VNTR regions (MS1-10) were revealed throughout the intronic and UTRs; seven VNTR regions were newly isolated and three VNTRs were previously reported...
January 5, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28038352/effects-of-decreased-dopamine-transporter-levels-on-nigrostriatal-neurons-and-paraquat-maneb-toxicity-in-mice
#10
Franziska Richter, Lauryn Gabby, Kimberly A McDowell, Caitlyn K Mulligan, Krystal De La Rosa, Pedrom C Sioshansi, Farzad Mortazavi, Ingrid Cely, Larry C Ackerson, Linda Tsan, Niall P Murphy, Nigel T Maidment, Marie-Françoise Chesselet
How genetic variations in the dopamine transporter (DAT) combined with exposure to environmental toxins modulate the risk of Parkinson's disease remains unclear. Using unbiased stereology in DAT knock-down mice (DAT-KD) and wild-type (WT) littermates, we found that decreased DAT caused a loss of tyrosine hydroxylase-positive (dopaminergic) neurons in subregions of the substantia nigra pars compacta at 3-4 days, 5 weeks, and 18 months of age. Both genotypes lost dopaminergic neurons with age and remaining neurons at 11 months were resilient to paraquat/maneb...
December 1, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28035426/diagnostic-imaging-of-dementia-with-lewy-bodies-by-susceptibility-weighted-imaging-of-nigrosomes-versus-striatal-dopamine-transporter-single-photon-emission-computed-tomography-a-retrospective-observational-study
#11
Koji Kamagata, Tomoya Nakatsuka, Ryuji Sakakibara, Yohei Tsuyusaki, Tomohiro Takamura, Kanako Sato, Michimasa Suzuki, Masaaki Hori, Kanako K Kumamaru, Tsutomu Inaoka, Shigeki Aoki, Hitoshi Terada
INTRODUCTION: The characteristics of dementia with Lewy bodies (DLB), Alzheimer's disease (AD) and amnestic mild cognitive impairment (a-MCI) overlap but require different treatments; therefore, it is important to differentiate these pathologies. Assessment of dopamine uptake in the striatum using dopamine transporter (DaT) single-photon emission computed tomography (SPECT) is the gold standard for diagnosing DLB; however, this modality is expensive, time consuming and involves radiation exposure...
January 2017: Neuroradiology
https://www.readbyqxmd.com/read/28031268/distinct-roles-of-opioid-and-dopamine-systems-in-lateral-hypothalamic-intracranial-self-stimulation
#12
Soichiro Ide, Takehiro Takahashi, Yukio Takamatsu, George R Uhl, Hiroaki Niki, Ichiro Sora, Kazutaka Ikeda
BACKGROUND: Opioid and dopamine systems play crucial roles in reward. Similarities and differences in the neural mechanisms of reward that are mediated by these two systems have remained largely unknown. Thus, in the present study, we investigated the differences in reward function in both µ-opioid receptor knockout (MOP KO) mice and dopamine transporter knockout (DAT KO) mice, important molecules in the opioid and dopamine systems. METHODS: Mice were implanted with electrodes into the right lateral hypothalamus (lh)...
December 28, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28031054/decreased-lymphocyte-dopamine-transporter-in-romantic-lovers
#13
Donatella Marazziti, Stefano Baroni, Gino Giannaccini, Armando Piccinni, Federico Mucci, Mario Catena-Dell'Osso, Grazia Rutigliano, Gabriele Massimetti, Liliana Dell'Osso
OBJECTIVE: The role of dopamine (DA) in romantic love is suggested by different evidence and is supported by the findings of some brain imaging studies. The DA transporter (DAT) is a key structure in regulating the concentration of the neurotransmitter in the synaptic cleft. Given the presence of DAT in blood cells, the present study aimed to explore it in resting lymphocytes of 30 healthy subjects of both sexes in the early stage of romantic love (no longer than 6 months), as compared with 30 subjects involved in a long-lasting relationship...
December 29, 2016: CNS Spectrums
https://www.readbyqxmd.com/read/28027110/unaltered-dopamine-transporter-availability-in-drug-naive-patients-with-schizophrenia-after-6-months-of-antipsychotics-treatment-a-naturalistic-study
#14
Wei Hung Chang, Kao Chin Chen, I Hui Lee, Mei Hung Chi, Po See Chen, Wei Jen Yao, Nan Tsing Chiu, Yen Kuang Yang
BACKGROUND: Dopaminergic dysfunction, namely, dopamine transporter (DAT) availability variations in patients with drug-naive schizophrenia after long-term treatment, is still not well understood. The aims of the study were to explore (i) whether the DAT availability in patients with drug-naive schizophrenia differed after antipsychotic treatment and (ii) whether treatment with different generations of antipsychotics influenced the DAT availability after follow-up for 6 months. METHODS: Twenty-four first-episode, drug-naive patients with schizophrenia were divided into first- and second-generation antipsychotic groups naturalistically...
February 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28006954/the-neuroprotective-effect-of-dimethyl-fumarate-in-a-mptp-mouse-model-of-parkinson-s-disease-involvement-of-reactive-oxygen-species-nuclear-factor-%C3%AE%C2%BAb-nuclear-transcription-factor-related-to-nf-e2
#15
Michela Campolo, Giovanna Casili, Flavia Biundo, Rosalia Crupi, Marika Cordaro, Salvatore Cuzzocrea, Emanuela Esposito
AIM: Oxidative stress plays a key role in Parkinson's disease (PD) and nuclear transcription factor related to NF-E2 (Nrf-2) is involved in neuroprotection against PD. The aim of the present study was to investigate the neurotherapeutic action, NF-κB/Nrf-2 dependent, of DMF in a mouse model of PD and in vitro SHSY-5Y cells. RESULTS: Daily oral gavage of DMF (10, 30 and 100 mg/kg) significantly reduced neuronal degeneration of dopaminergic tract and behavioral impairments induced by four injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
December 23, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27995072/application-of-texture-analysis-to-dat-spect-imaging-relationship-to-clinical-assessments
#16
Arman Rahmim, Yousef Salimpour, Saurabh Jain, Stephan A L Blinder, Ivan S Klyuzhin, Gwenn S Smith, Zoltan Mari, Vesna Sossi
Dopamine transporter (DAT) SPECT imaging is increasingly utilized for diagnostic purposes in suspected Parkinsonian syndromes. We performed a cross-sectional study to investigate whether assessment of texture in DAT SPECT radiotracer uptake enables enhanced correlations with severity of motor and cognitive symptoms in Parkinson's disease (PD), with the long-term goal of enabling clinical utility of DAT SPECT imaging, beyond standard diagnostic tasks, to tracking of progression in PD. Quantitative analysis in routine DAT SPECT imaging, if performed at all, has been restricted to assessment of mean regional uptake...
2016: NeuroImage: Clinical
https://www.readbyqxmd.com/read/27990313/deep-brain-stimulation-of-a-patient-with-psychogenic-movement-disorder
#17
Jean-Philippe Langevin, Jesse M Skoch, Scott J Sherman
BACKGROUND: The long-term safety of deep brain stimulation (DBS) is an important issue because new applications are being investigated for a variety of disorders. Studying instances where DBS was inadvertently implanted in patients without a movement disorder may provide information about the safety of the therapy. We report the case of a patient with a psychogenic movement disorder treated with deep brain stimulation (DBS). CASE DESCRIPTION: The patient presented at our clinic after 5 years of chronic DBS of the subthalamic nucleus (STN) for presumed Parkinson's disease...
2016: Surgical Neurology International
https://www.readbyqxmd.com/read/27989490/paraphilic-sexual-offenders-do-not-differ-from-control-subjects-with-respect-to-dopamine-and-serotonin-related-genetic-polymorphisms
#18
Andrzej Jakubczyk, Aleksandra Krasowska, Marcin Bugaj, Maciej Kopera, Anna Klimkiewicz, Agata Łoczewska, Aneta Michalska, Aleksandra Majewska, Natalia Szejko, Anna Podgórska, Małgorzata Sołowiej, Leszek Markuszewski, Sławomir Jakima, Rafał Płoski, Kirk Brower, Marcin Wojnar
INTRODUCTION: Rape and pedophilic child molestation are the most commonly convicted sexual offenses in Poland. Recent studies have suggested a possible genetic contribution toward pathologic sexual interests and behaviors. AIM: To analyze and compare functional polymorphisms of genes associated with the activity of the serotonin and dopamine systems in a group of paraphilic sexual offenders and control subjects. METHODS: The study sample (n = 97) consisted of two groups: paraphilic sexual offenders (65 pedophilic child molesters and 32 rapists) and controls (n = 76)...
December 15, 2016: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/27986813/dopamine-transporter-amino-and-carboxy-termini-synergistically-contribute-to-substrate-and-inhibitor-affinities
#19
Carolyn G Sweeney, Bradford P Tremblay, Thomas Stockner, Harald H Sitte, Haley E Melikian
Extracellular dopamine and serotonin concentrations are determined by the presynaptic dopamine (DAT) and serotonin (SERT) transporters, respectively. Numerous studies have investigated the DAT and SERT structural elements contributing to inhibitor and substrate binding. To date, crystallographic studies have focused on conserved transmembrane domains, where multiple substrate binding and translocation features are conserved. However, it is unknown what, if any, role the highly divergent intracellular amino and carboxy termini contribute to these processes...
December 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27981196/social-defeat-stress-induces-depression-like-behavior-and-alters-spine-morphology-in-the-hippocampus-of-adolescent-male-c57bl-6-mice
#20
Sergio D Iñiguez, Antonio Aubry, Lace M Riggs, Jason B Alipio, Roseanna M Zanca, Francisco J Flores-Ramirez, Mirella A Hernandez, Steven J Nieto, David Musheyev, Peter A Serrano
Social stress, including bullying during adolescence, is a risk factor for common psychopathologies such as depression. To investigate the neural mechanisms associated with juvenile social stress-induced mood-related endophenotypes, we examined the behavioral, morphological, and biochemical effects of the social defeat stress model of depression on hippocampal dendritic spines within the CA1 stratum radiatum. Adolescent (postnatal day 35) male C57BL/6 mice were subjected to defeat episodes for 10 consecutive days...
December 2016: Neurobiology of Stress
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