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Serotonin transporter

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https://www.readbyqxmd.com/read/28534451/genetic-moderation-of-multiple-pathways-linking-early-cumulative-socioeconomic-adversity-and-young-adults-cardiometabolic-disease-risk
#1
Kandauda A S Wickrama, Tae Kyoung Lee, Catherine Walker O'Neal
Recent research suggests that psychosocial resources and life stressors are mediating pathways explaining socioeconomic variation in young adults' health risks. However, less research has examined both these pathways simultaneously and their genetic moderation. A nationally representative sample of 11,030 respondents with prospective data collected over 13 years from the National Study of Adolescent to Adult Health was examined. First, the association between early cumulative socioeconomic adversity and young adults' (ages 25-34) cardiometabolic disease risk, as measured by 10 biomarkers, through psychosocial resources (educational attainment) and life stressors (accelerated transition to adulthood) was examined...
May 23, 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/28533695/the-triallelic-serotonin-transporter-gene-polymorphism-is-associated-with-depressive-symptoms-in-adults-with-chronic-pain
#2
W Michael Hooten, Cynthia O Townsend, Christopher D Sletten
BACKGROUND: The serotonin (5-HT) transporter-linked polymorphic region (5-HTTLPR) moderates the relationship between stressful life events and depression. Given the high prevalence of depression in chronic pain, the primary aim of this preliminary study was to investigate the associations between the 5-HTTLPR and the severity of depressive symptoms in a cohort of adults with chronic pain. METHODS: Adults with chronic pain who were consecutively admitted to an outpatient pain rehabilitation program and met inclusion criteria were recruited for study participation (n=277)...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28530234/n-alkylated-analogs-of-4-methylamphetamine-4-ma-differentially-affect-monoamine-transporters-and-abuse-liability
#3
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/28528967/chronic-fluoxetine-rescues-changes-in-plasma-membrane-density-of-5-ht1a-autoreceptors-and-serotonin-transporters-in-the-olfactory-bulbectomy-rodent-model-of-depression
#4
Mustapha Riad, Antonia Kobert, Laurent Descarries, Sandra Boye, Pierre-Paul Rompré, Jean-Claude Lacaille
Reduced serotonin (5-HT) neurotransmission is postulated to underlie the pathogenesis of depression. The serotonin transporter (SERT) and 5-HT1A auto-receptors act in concert to ensure homeostasis of serotonin (5-HT) neurotransmission and regulation of their cell surface expression represent efficient mechanisms to maintain this homeostasis. Thus, we investigated the changes in the subcellular distribution of SERT and 5-HT1A receptors (5-HT1AR) in the rat olfactory bulbectomy model of depression using immuno-gold labelling and electron microscopy, and examined the effect of chronic treatment with the antidepressant, fluoxetine, a serotonin reuptake inhibitor, on the subcellular distribution of SERT and 5-HT1AR...
May 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28528289/platelet-hyperactivation-apoptosis-and-hypercoagulability-in-patients-with-acute-pulmonary-embolism
#5
Samin Rezania, Michael A Puskarich, Daniela N Petrusca, Evandro M Neto-Neves, Matthew T Rondina, Jeffrey A Kline
Changes in systemic redox balance can alter platelet activation and aggregation. Acute pulmonary embolism (PE) is a systematic inflammatory disease associated with mechanical shear stress, increased thrombin, catecholamines, serotonin and hemolysis, which cumulatively can hyperactivate platelets and accelerate their turnover. We tested the hypothesis that platelets from patients with moderately severe PE will show hyperstimulation and a pre-apoptotic phenotype associated with microparticles (MPs) in plasma...
May 13, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28512029/calixarene-mediated-liquid-membrane-transport-of-choline-conjugates-3-the-effect-of-handle-variation-on-neurotransmitter-transport
#6
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/28511918/molecular-imaging-of-serotonin-degeneration-in-mild-cognitive-impairment
#7
Gwenn S Smith, Frederick S Barrett, Jin Hui Joo, Najlla Nassery, Alena Savonenko, Devin J Sodums, Christopher M Marano, Cynthia A Munro, Jason Brandt, Michael A Kraut, Yun Zhou, Dean F Wong, Clifford I Workman
Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions, as well as the cell bodies of origin (raphe nuclei)...
May 13, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28504644/direct-reconstruction-of-parametric-images-for-brain-pet-with-event-by-event-motion-correction-evaluation-in-two-tracers-across-count-levels
#8
Mary Germino, Jean-Dominique Gallezot, Jianhua Yan, Richard Carson
Parametric images for dynamic positron emission tomography (PET) are typically generated by an indirect method, i.e., reconstructing a time series of emission images, then fitting a kinetic model to each voxel time activity curve. Alternatively, "direct reconstruction," incorporates the kinetic model into the reconstruction algorithm itself, directly producing parametric images from projection data. Direct reconstruction has been shown to achieve parametric images with lower standard error than the indirect method...
May 15, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28503727/serotonin-norepinephrine-reuptake-inhibitors-and-the-influence-of-binding-affinity-ki-on-analgesia
#9
M Raouf, A J Glogowski, J J Bettinger, J Fudin
WHAT IS KNOWN AND OBJECTIVE: Serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used for various psychiatric conditions and neuropathic pain syndromes. SNRIs inhibit the reuptake of serotonin (5-HT) and norepinephrine (NE); however, NE reuptake inhibition is thought to be the primary mediator for their analgesic effect. COMMENT: Key differences in pharmacodynamics and receptor affinities exist between SNRIs. The selectivity for each monoamine differs among SNRIs based on the agent's affinity and activity at the monoamine reuptake transporter...
May 15, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28501470/possibility-of-predicting-sert-occupancy-from-the-in-vitro-inhibition-constant-for-sert-the-clinically-relevant-plasma-concentration-of-unbound-drugs-and-their-profiles-for-substrates-of-transporters
#10
REVIEW
Masahiro Yahata, Koji Chiba, Takao Watanabe, Yuichi Sugiyama
Accurate prediction of target occupancy facilitates CNS drug development. In this review, we discuss the predictability of serotonin transporter (SERT) occupancy in human brain estimated from in vitro Ki values for human SERT and plasma concentrations of unbound drug (Cu,plasma) as well as the impact of drug transporters in the blood-brain barrier. First, the geometric means of in vitro Ki values were compared with the means of in vivo Ki values (Ki,u,plasma) which were calculated as Cu,plasma values at 50% occupancy of SERT obtained from previous clinical PET/SPECT imaging studies for 6 selective serotonin transporter reuptake inhibitors (SSRIs) and 3 serotonin norepinephrine reuptake inhibitors (SNRIs)...
May 10, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28499269/identification-of-novel-serotonin-reuptake-inhibitors-targeting-central-and-allosteric-binding-sites-a-virtual-screening-and-molecular-dynamics-simulations-study
#11
Ismail Erol, Busecan Aksoydan, Isik Kantarcioglu, Ramin E Salmas, Serdar Durdagi
The serotonin (5-hydroxytryptamine, 5HT) transporter (SERT) is a member of neurotransmitter sodium symporter (NSS) family, which maintains neurotransmitter by reuptaking 5HT into synapses. Decrease in serotonin concentrations in synaptic clefts have been reported to cause psychological and neurological disorders. Therefore, inhibition of SERT is a potent strategy for the treatment of related diseases such as depression. In this study, approximately 260,000 small molecules from an available chemical database have been virtually screened both at central and allosteric binding sites of SERT to identify potent novel candidate SERT inhibitors...
March 22, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28499187/vortioxetine-a-review-of-the-pharmacology-and-clinical-profile-of-the-novel-antidepressant
#12
REVIEW
Magdalena Sowa-Kućma, Patrycja Pańczyszyn-Trzewik, Paulina Misztak, Rafał R Jaeschke, Katherine Sendek, Krzysztof Styczeń, Wojciech Datka, Magdalena Koperny
The aim of this paper was to review the up-to-date evidence base on pharmacology and clinical properties of vortioxetine. Vortioxetine is a novel antidepressant, approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). Because vortioxetine exhibits both an antidepressant and anxiolytic effect, it may be effective in treating both depressive and anxiety disorders, such as generalized anxiety disorder (GAD). Based on its pharmacodynamics profile and preclinical studies, it is believe that the drug's clinical action is mediated mainly by selective blockade of serotonin reuptake (by inhibiting the serotonin transporter [SERT]) and direct modulation of 5-HT receptors activity (such as 5-HT3, 5-HT7, 5-HT1D and 5-HT1B)...
February 1, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28491024/the-serotonin-transporter-and-early-life-stress-translational-perspectives
#13
REVIEW
Danielle J Houwing, Bauke Buwalda, Eddy A van der Zee, Sietse F de Boer, Jocelien D A Olivier
The interaction between the serotonin transporter (SERT) linked polymorphic region (5-HTTLPR) and adverse early life stressing (ELS) events is associated with enhanced stress susceptibility and risk to develop mental disorders like major depression, anxiety, and aggressiveness. In particular, human short allele carriers are at increased risk. This 5-HTTLPR polymorphism is absent in the rodent SERT gene, but heterozygous SERT knockout rodents (SERT(+/-)) show several similarities to the human S-allele carrier, therefore creating an animal model of the human situation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28486929/ulk1-phosphorylates-sec23a-and-mediates-autophagy-induced-inhibition-of-er-to-golgi-traffic
#14
Wenjia Gan, Caiyun Zhang, Ka Yu Siu, Ayano Satoh, Julian A Tanner, Sidney Yu
BACKGROUND: Autophagy is an inducible autodigestive process that allows cells to recycle proteins and other materials for survival during stress and nutrient deprived conditions. The kinase ULK1 is required to activate this process. ULK1 phosphorylates a number of target proteins and regulates many cellular processes including the early secretory pathway. Recently, ULK1 has been demonstrated to phosphorylate Sec16 and affects the transport of serotonin transporter at the ER exit sites (ERES), but whether ULK1 may affect the transport of other cargo proteins and general secretion has not been fully addressed...
May 10, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28485065/heterogeneity-of-enterochromaffin-cells-within-the-gastrointestinal-tract
#15
REVIEW
S Diwakarla, L J Fothergill, J Fakhry, B Callaghan, J B Furness
Enterochromaffin cells were the first endocrine cells of the gastrointestinal tract to be chemically distinguished, almost 150 years ago. It is now known that the chromaffin reaction of these cells was due to their content of the reactive aromatic amine, 5-hydroxytryptamine (5-HT, also known as serotonin). They have commonly been thought to be a special class of gut endocrine cells (enteroendocrine cells) that are distinct from the enteroendocrine cells that contain peptide hormones. The study by Martin et al...
June 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28485037/serotonin-axons-in-the-neocortex-of-the-adult-female-mouse-regrow-after-traumatic-brain-injury
#16
Tymoteusz J Kajstura, Sarah E Dougherty, David J Linden
It is widely held that injured neurons in the central nervous system do not undergo axonal regrowth. However, there is mounting evidence that serotonin axons are a notable exception. Serotonin axons undergo long-distance regrowth in the neocortex after amphetamine lesion, and, following a penetrating stab injury, they can regrow from cut ends to traverse the stab rift. Traumatic brain injury (TBI) is clinically prevalent and can lead to pathologies, such as depression, that are related to serotonergic dysfunction...
May 9, 2017: Journal of Neuroscience Research
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/28473438/serotonin-signaling-through-the-5-ht1b-receptor-and-nadph-oxidase-1-in-pulmonary-arterial-hypertension
#19
Katie Y Hood, Kirsty M Mair, Adam P Harvey, Augusto C Montezano, Rhian M Touyz, Margaret R MacLean
OBJECTIVE: Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesize that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase-derived ROS generation and reduced Nrf-2 (nuclear factor (erythroid-derived 2)-like 2) antioxidant systems, promoting vascular injury. APPROACH AND RESULTS: HPASMCs from controls and PAH patients, and PASMCs from Nox1(-)(/-) mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT1B receptor, and NADPH oxidase 1 (Nox1)...
May 4, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28467954/-association-between-the-5-httlpr-polymorphism-of-the-serotonin-transporter-gene-and-suicide-a-case-control-pilot-study
#20
Janos Bokor, Xenia Gonda, Peter Dome, Gabor Faludi, Elek Dinya, Andras Laszik
OBJECTIVES: Besides psychological and social effects, biological, biochemical and genetic factors also play a role in the background of suicide. The aim is developing a complex model incorporating all the above factors so that suicide could be predicted and prevented in those at risk. Based on several studies 5-HTTLPR s allele frequency is increased in case of violent completed suicides. The aim of the present study was to validate this association in a sample of completed suicides. METHODS: During autopsy sample DNA samples were obtained for 5-HTTLPR genotyping from 200 subjects deceased due to suicide and 200 controls deceased due to other causes...
March 2017: Neuropsychopharmacologia Hungarica
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