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Dopamine transporter

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https://www.readbyqxmd.com/read/28549646/increased-central-dopaminergic-activity-might-be-involved-in-the-behavioral-abnormality-of-cuprizone-exposure-mice
#1
Haoxiao Chang, Jianghong Liu, Yifan Zhang, Fang Wang, Yanchuan Wu, Li Zhang, Houxi Ai, Guangliang Chen, Linlin Yin
The neurotoxican cuprizone (CPZ, a copper chelator) has been used extensively to create a mouse model of demyelination. However, the effects on behavior of CPZ treatment have not been reported in C57BL/6 mice given a diet containing 0.4% CPZ within 3weeks. Behavioral abnormalities were assessed using a range of test: Y-maze, spontaneous locomotor activity, rota-rod test, novel object recognition, climbing. Mice exposed to CPZ displayed more arm entrance, locomotor movements, and climbing behavior, suggesting an increase in central nervous system activity...
May 23, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28548869/neurotransmitter-receptor-availability-in-the-rat-brain-is-constant-in-a-24-hour-period
#2
A Oskamp, F Wedekind, T Kroll, D Elmenhorst, A Bauer
Wakefulness and sleep are fundamental characteristics of the brain. We, therefore, hypothesized that transmitter systems contribute to their regulation and will exhibit circadian alterations. We assessed the concentration of various neurotransmitter receptors and transporters including adenosinergic (A1AR, A2AAR, and ENT1), dopaminergic (D1R, D2R, and DAT), and serotonergic (5-HT2AR) target proteins. Adult male Sprague Dawley rats were used and maintained in a 12 h light: 12 h dark cycle (lights on from 07:00 h to 19:00 h)...
May 26, 2017: Chronobiology International
https://www.readbyqxmd.com/read/28542144/dicer-and-micrornas-protect-adult-dopamine-neurons
#3
Piotr Chmielarz, Julia Konovalova, Syeda Sadia Najam, Heike Alter, Timo Petteri Piepponen, Holger Erfle, Kai C Sonntag, Günther Schütz, Ilya A Vinnikov, Andrii Domanskyi
MicroRNAs (miRs) are important post-transcriptional regulators of gene expression implicated in neuronal development, differentiation, aging and neurodegenerative diseases, including Parkinson's disease (PD). Several miRs have been linked to PD-associated genes, apoptosis and stress response pathways, suggesting that deregulation of miRs may contribute to the development of the neurodegenerative phenotype. Here, we investigate the cell-autonomous role of miR processing RNAse Dicer in the functional maintenance of adult dopamine (DA) neurons...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28537985/neuroimaging-in-parkinson-s-disease-focus-on-substantia-nigra-and-nigro-striatal-projection
#4
Daniela Frosini, Mirco Cosottini, Duccio Volterrani, Roberto Ceravolo
PURPOSE OF REVIEW: The diagnosis of Parkinson disease is based on clinical features; however, unmet need is an imaging signature for Parkinson disease and the early differential diagnosis with atypical parkinsonisms. A summary of the molecular imaging and MRI recent evidences for Parkinson disease diagnosis will be presented in this review. RECENT FINDINGS: The nigro-striatal dysfunction explored by dopamine transporter imaging is not a mandatory diagnostic criterion for Parkinson disease, recent evidence supported its utility as in-vivo proof of degenerative parkinsonisms, and there might be compensatory mechanisms leading to an early overestimation...
May 22, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28535798/using-kalirin-conditional-knockout-mice-to-distinguish-its-role-in-dopamine-receptor-mediated-behaviors
#5
Taylor P LaRese, Yan Yan, Betty A Eipper, Richard E Mains
BACKGROUND: Mice lacking Kalirin-7 (Kal7(KO)), a Rho GDP/GTP exchange factor, self-administer cocaine at a higher rate than wildtype mice, and show an exaggerated locomotor response to experimenter-administered cocaine. Kal7, which localizes to post-synaptic densities at glutamatergic synapses, interacts directly with the GluN2B subunit of the N-methyl-D-aspartate (NMDA; GluN) receptor. Consistent with these observations, Kal7 plays an essential role in NMDA receptor dependent long term potentiation and depression, and glutamatergic transmission plays a key role in the response to chronic cocaine...
May 23, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28534083/synthetic-alpha-synuclein-fibrils-cause-mitochondrial-impairment-and-selective-dopamine-neurodegeneration-in-part-via-inos-mediated-nitric-oxide-production
#6
Victor Tapias, Xiaoping Hu, Kelvin C Luk, Laurie H Sanders, Virginia M Lee, J Timothy Greenamyre
Intracellular accumulation of α-synuclein (α-syn) are hallmarks of synucleinopathies, including Parkinson's disease (PD). Exogenous addition of preformed α-syn fibrils (PFFs) into primary hippocampal neurons induced α-syn aggregation and accumulation. Likewise, intrastriatal inoculation of PFFs into mice and non-human primates generates Lewy bodies and Lewy neurites associated with PD-like neurodegeneration. Herein, we investigate the putative effects of synthetic human PFFs on cultured rat ventral midbrain dopamine (DA) neurons...
May 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28530234/n-alkylated-analogs-of-4-methylamphetamine-4-ma-differentially-affect-monoamine-transporters-and-abuse-liability
#7
Ernesto Solis, John S Partilla, Farhana Sakloth, Iwona Ruchala, Kathryn L Schwienteck, Louis J De Felice, Jose M Eltit, Richard A Glennon, S Stevens Negus, Michael H Baumann
Clandestine chemists synthesize novel stimulant drugs by exploiting structural templates known to target monoamine transporters for dopamine, norepinephrine and serotonin (DAT, NET, and SERT, respectively). 4-Methylamphetamine (4-MA) is an emerging drug of abuse that interacts with transporters, but limited structure-activity data are available for its analogs. Here we employed uptake and release assays in rat brain synaptosomes, voltage-clamp current measurements in cells expressing transporters, and calcium flux assays in cells co-expressing transporters and calcium channels to study the effects of increasing N-alkyl chain length of 4-MA on interactions at DAT, NET and SERT...
May 22, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28527958/treadmill-exercise-produces-neuroprotective-effects-in-a-murine-model-of-parkinson-s-disease-by-regulating-the-tlr2-myd88-nf-%C3%AE%C2%BAb-signaling-pathway
#8
Jung-Hoon Koo, Yong-Chul Jang, Dong-Ju Hwang, Hyun-Seob Um, Nam-Hee Lee, Jae-Hoon Jung, Joon-Yong Cho
Parkinson's disease (PD) is characterized by progressive dopamine depletion and a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Treadmill exercise is a promising non-pharmacological approach for reducing the risk of PD and other neuroinflammatory disorders, such as Alzheimer's disease. The goal of this study was to investigate the effects of treadmill exercise on α-synuclein-induced neuroinflammation and neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28520803/multiple-modality-biomarker-prediction-of-cognitive-impairment-in-prospectively-followed-de-novo-parkinson-disease
#9
Chelsea Caspell-Garcia, Tanya Simuni, Duygu Tosun-Turgut, I-Wei Wu, Yu Zhang, Mike Nalls, Andrew Singleton, Leslie A Shaw, Ju-Hee Kang, John Q Trojanowski, Andrew Siderowf, Christopher Coffey, Shirley Lasch, Dag Aarsland, David Burn, Lana M Chahine, Alberto J Espay, Eric D Foster, Keith A Hawkins, Irene Litvan, Irene Richard, Daniel Weintraub
OBJECTIVES: To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments. METHODS: We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition...
2017: PloS One
https://www.readbyqxmd.com/read/28515088/loss-of-nherf-1-expression-prevents-dopamine-mediated-na-k-atpase-regulation-in-renal-proximal-tubule-cells-from-rat-models-of-hypertension-aged-f344-and-shrs
#10
Michelle T Barati, Corey J Ketchem, Michael L Merchant, Walter B Kusiak, Pedro A Jose, Edward J Weinman, Amanda J LeBlanc, Eleanor D Lederer, Syed J Khundmiri
Dopamine decreases Na-K ATPase (NKA) activity by PKC-dependent phosphorylation and endocytosis of the NKA alpha1. Dopamine-mediated regulation of NKA is impaired in aging and some forms of hypertension. Using opossum (OK) proximal tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) associates with NKA alpha1 and dopamine-1 receptor (D1R). This association is required for the dopamine-mediated regulation of NKA. In OK cells dopamine decreases NHERF-1 association with NKA alpha1 but increases its association with D1R...
May 17, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28512029/calixarene-mediated-liquid-membrane-transport-of-choline-conjugates-3-the-effect-of-handle-variation-on-neurotransmitter-transport
#11
James L Collins, Ayu Fujii, Sahar Roshandel, Cuong-Alexander To, Michael P Schramm
Upper rim phosphonic acid functionalized calix[4]arene affects selective transport of multiple molecular payloads through a liquid membrane. The secret is in the attachment of a receptor-complementary handle to the payload. We find that the trimethylammonium ethylene group present in choline is one of several general handles for the transport of drug and drug-like species. Herein we compare the effect of handle variation against the transport of serotonin and dopamine. We find that several ionizable amine termini handles are sufficient for transport and identify two ideal candidates...
May 5, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28507136/ocd-candidate-gene-slc1a1-eaat3-impacts-basal-ganglia-mediated-activity-and-stereotypic-behavior
#12
Isaac D Zike, Muhammad O Chohan, Jared M Kopelman, Emily N Krasnow, Daniel Flicker, Katherine M Nautiyal, Michael Bubser, Christoph Kellendonk, Carrie K Jones, Gregg Stanwood, Kenji Fransis Tanaka, Holly Moore, Susanne E Ahmari, Jeremy Veenstra-VanderWeele
Obsessive-compulsive disorder (OCD) is a chronic, disabling condition with inadequate treatment options that leave most patients with substantial residual symptoms. Structural, neurochemical, and behavioral findings point to a significant role for basal ganglia circuits and for the glutamate system in OCD. Genetic linkage and association studies in OCD point to SLC1A1, which encodes the neuronal glutamate/aspartate/cysteine transporter excitatory amino acid transporter 3 (EAAT3)/excitatory amino acid transporter 1 (EAAC1)...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28499878/possible-role-of-organic-cation-transporters-in-the-distribution-of-11-c-sulpiride-a-dopamine-d2-receptor-antagonist
#13
Harumasa Takano, Sumito Ito, Xuan Zhang, Hiroshi Ito, Ming-Rong Zhang, Hiroshi Suzuki, Kazuya Maeda, Hiroyuki Kusuhara, Tetsuya Suhara, Yuichi Sugiyama
We synthesized [(11)C]sulpiride as a positron emission tomography (PET) probe for investigating the drug distribution in the human body. [(11)C]Sulpiride was injected to healthy male subjects in either tracer dose of [(11)C]sulpiride (ca 222 MBq) or with therapeutic dose of sulpiride (500 mg, po) 3 hours prior to the injection in a crossover fashion. Whole body PET imaging demonstrated that [(11)C]sulpiride accumulated exceedingly in the bladder, followed by liver, gall bladder and kidney respectively; at 30 minutes after the injection, whereas scarcely in the brain...
May 9, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28498499/heterogeneous-extracellular-dopamine-regulation-in-the-subregions-of-the-olfactory-tubercle
#14
Jinwoo Park, Ken T Wakabayashi, Caitlin Szalkowski, Rohan V Bhimani
Recent studies show that dense dopamine (DA) innervation from the ventral tegmental area (VTA) to the olfactory tubercle (OT) may play an important role in processing multisensory information pertaining to arousal and reward, yet little is known about DA regulation in the OT. This is mainly due to the anatomical limitations of conventional methods of determining DA dynamics in small heterogeneous OT subregions located in the ventral most part of the brain. Additionally, there is increasing awareness that anteromedial and anterolateral subregions of the OT have distinct functional roles in natural and psychostimulant drug reinforcement as well as in regulating other types of behavioral responses, such as aversion...
May 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28495886/the-sigma-1-receptor-modulates-dopamine-transporter-conformation-and-cocaine-binding-and-may-thereby-potentiate-cocaine-self-administration-in-rats
#15
Weimin Conrad Hong, Hideaki Yano, Takato Hiranita, Frederick T Chin, Christopher R McCurdy, Tsung-Ping Su, Susan G Amara, Jonathan L Katz
The dopamine transporter (DAT) regulates dopamine (DA) neurotransmission by recapturing DA into the presynaptic terminals, and is a principal target of the psychostimulant cocaine. The sigma-1 receptor (σ1R) is a molecular chaperone, and its ligands have been shown to modulate dopamine neuronal signaling, although their effects on DAT activity are unclear. Here, we report that the prototypical σ1R agonist (+)-pentazocine potentiated the dose response of cocaine self-administration in rats, consistent with effects of the σR agonists PRE-084 and DTG reported previously...
May 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28492278/direct-and-systemic-administration-of-a-cns-permeant-tamoxifen-analog-reduces-amphetamine-induced-dopamine-release-and-reinforcing-effects
#16
Colleen Carpenter, Alexander G Zestos, Rachel Altshuler, Roderick J Sorenson, Bipasha Guptaroy, Hollis D Showalter, Robert T Kennedy, Emily Jutkiewicz, Margaret E Gnegy
Amphetamines (AMPHs) are globally abused. With no effective treatment for AMPH addiction to date, there is urgent need for the identification of druggable targets that mediate the reinforcing action of this stimulant class. AMPH-stimulated dopamine efflux is modulated by protein kinase C (PKC) activation. Inhibition of PKC reduces AMPH-stimulated dopamine efflux and locomotor activity. The only known CNS-permeant PKC inhibitor is the selective estrogen receptor modulator tamoxifen. In this study we demonstrate that a tamoxifen analog, 6c, which more potently inhibits PKC than tamoxifen but lacks affinity for the estrogen receptor, reduces AMPH-stimulated increases in extracellular dopamine and reinforcement-related behavior...
May 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28480332/label-free-detection-of-small-organic-molecules-by-molecularly-imprinted-polymer-functionalized-thermocouples-toward-in-vivo-applications
#17
Hanne Diliën, Marloes Peeters, Jeroen Royakkers, Jules Harings, Peter Cornelis, Patrick Wagner, Erik Steen Redeker, Craig E Banks, Kasper Eersels, Bart van Grinsven, Thomas J Cleij
Molecularly imprinted polymers (MIPs), synthetic polymeric receptors, have been combined successfully with thermal transducers for the detection of small molecules in recent years. However, up until now they have been combined with planar electrodes which limits their use for in vivo applications. In this work, a new biosensor platform is developed by roll-coating MIP particles onto thermocouples, functionalized with polylactic acid (PLLA). As a first proof-of-principle, MIPs for the neurotransmitter dopamine were incorporated into PLLA-coated thermocouples...
April 28, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28479505/effects-of-monocrotophos-pesticide-on-cholinergic-and-dopaminergic-neurotransmitter-systems-during-early-development-in-the-sea-urchin-hemicentrotus-pulcherrimus
#18
Xiaona Zhang, Shuman Li, Cuicui Wang, Hua Tian, Wei Wang, Shaoguo Ru
During early development in sea urchins, classical neurotransmitters, including acetylcholine (ACh), dopamine (DA), and serotonin (5-HT), play important roles in the regulation of morphogenesis and swimming behavior. However, the underlying mechanisms of how organophosphate pesticides cause developmental neurotoxicity by interfering with different neurotransmitter systems are unclear. In this study, we investigated the effects of 0.01, 0.10, and 1.00mg/L monocrotophos (MCP) pesticide on the activity of acetyltransferase (ChAT), acetylcholinesterase (AChE), monoamine oxidase, the concentration of DA, dopamine transporter, and the transcription activity of DA receptor D1 and tyrosine hydroxylase, during critical periods in cholinergic and dopaminergic nervous system development in sea urchin (Hemicentrotus pulcherrimus) embryos and larvae...
May 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28471062/pharmacologically-increasing-microtubule-acetylation-corrects-stress-exacerbated-effects-of-organophosphates-on-neurons
#19
Anand N Rao, Ankita Patil, Zachary D Brodnik, Liang Qiang, Rodrigo A España, Kimberly A Sullivan, Mark M Black, Peter W Baas
Many veterans of the 1990-1991 Gulf War contracted Gulf War Illness (GWI), a multisymptom disease that primarily affects the nervous system. Here, we treated cultures of human or rat neurons with diisopropyl fluorophosphate (DFP), an analog of sarin, one of the organophosphate (OP) toxicants to which the military veterans were exposed. All observed cellular defects produced by DFP were exacerbated by pretreatment with corticosterone or cortisol, which, in rat and human neurons, respectively, serves in our experiments to mimic the physical stress endured by soldiers during the war...
May 4, 2017: Traffic
https://www.readbyqxmd.com/read/28466092/repeated-social-defeat-and-the-rewarding-effects-of-cocaine-in-adult-and-adolescent-mice-dopamine-transcription-factors-probdnf-signaling-pathways-and-the-trkb-receptor-in-the-mesolimbic-system
#20
Sandra Montagud-Romero, Cristina Nuñez, M Carmen Blanco-Gandia, Elena Martínez-Laorden, María A Aguilar, Javier Navarro-Zaragoza, Pilar Almela, Maria-Victoria Milanés, María-Luisa Laorden, José Miñarro, Marta Rodríguez-Arias
RATIONALE: Repeated social defeat (RSD) increases the rewarding effects of cocaine in adolescent and adult rodents. OBJECTIVE: The aim of the present study was to compare the long-term effects of RSD on the conditioned rewarding effects of cocaine and levels of the transcription factors Pitx3 and Nurr1 in the ventral tegmental area (VTA), the dopamine transporter (DAT), the D2 dopamine receptor (D2DR) and precursor of brain-derived neurotrophic factor (proBDNF) signaling pathways, and the tropomyosin-related kinase B (TrkB) receptor in the nucleus accumbens (NAc) in adult and adolescent mice...
May 2, 2017: Psychopharmacology
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