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Serotonin transporter

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https://www.readbyqxmd.com/read/29164729/identification-and-characterization-of-a-histamine-binding-lipocalin-like-molecule-from-the-relapsing-fever-tick-ornithodoros-turicata
#1
G Neelakanta, H Sultana, D E Sonenshine, J F Andersen
Lipocalins are low molecular weight membrane transporters that are abundantly expressed in the salivary glands and other tissues of ticks. In this study, we identified a lipocalin-like molecule, designated as otlip, from the soft ticks Ornithodoros turicata, the vector for the relapsing fever causing spirochete Borrelia turicatae. We noted that the expression of otlip was developmentally regulated, with adult ticks expressing significantly higher levels in comparison to the larvae or nymphal ticks. Expression of otlip was evident in both fed and unfed O...
November 22, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/29163124/the-search-for-an-effective-therapy-to-treat-fragile-x-syndrome-dream-or-reality
#2
REVIEW
Sara Castagnola, Barbara Bardoni, Thomas Maurin
Fragile X Syndrome (FXS) is the most common form of intellectual disability and a primary cause of autism. It originates from the lack of the Fragile X Mental Retardation Protein (FMRP), which is an RNA-binding protein encoded by the Fragile X Mental Retardation Gene 1 (FMR1) gene. Multiple roles have been attributed to this protein, ranging from RNA transport (from the nucleus to the cytoplasm, but also along neurites) to translational control of mRNAs. Over the last 20 years many studies have found a large number of FMRP mRNA targets, but it is still not clear which are those playing a critical role in the etiology of FXS...
2017: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/29163018/brain-networks-implicated-in-seasonal-affective-disorder-a-neuroimaging-pet-study-of-the-serotonin-transporter
#3
Martin Nørgaard, Melanie Ganz, Claus Svarer, Patrick M Fisher, Nathan W Churchill, Vincent Beliveau, Cheryl Grady, Stephen C Strother, Gitte M Knudsen
Background: Seasonal Affective Disorder (SAD) is a subtype of Major Depressive Disorder characterized by seasonally occurring depression that often presents with atypical vegetative symptoms such as hypersomnia and carbohydrate craving. It has recently been shown that unlike healthy people, patients with SAD fail to globally downregulate their cerebral serotonin transporter (5-HTT) in winter, and that this effect seemed to be particularly pronounced in female S-carriers of the 5-HTTLPR genotype. The purpose of this study was to identify a 5-HTT brain network that accounts for the adaption to the environmental stressor of winter in females with the short 5-HTTLPR genotype, a specific subgroup previously reported to be at increased risk for developing SAD...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29162172/cumulative-prenatal-exposure-to-adversity-reveals-associations-with-a-broad-range-of-neurodevelopmental-outcomes-that-are-moderated-by-a-novel-biologically-informed-polygenetic-score-based-on-the-serotonin-transporter-solute-carrier-family-c6-member-4-slc6a4
#4
Patrícia P Silveira, Irina Pokhvisneva, Carine Parent, Shirong Cai, Anu Sathyan Sathyapalan Rema, Birit F P Broekman, Anne Rifkin-Graboi, Michael Pluess, Kieran J O'Donnell, Michael J Meaney
While many studies focus on the association between early life adversity and the later risk for psychopathology, few simultaneously explore diverse forms of environmental adversity. Moreover, those studies that examined the cumulative impact of early life adversity focus uniquely on postnatal influences. The objective of this study was to focus on the fetal period of development to construct and validate a cumulative prenatal adversity score in relation to a wide range of neurodevelopmental outcomes. We also examined the interaction of this adversity score with a biologically informed genetic score based on the serotonin transporter gene...
December 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/29153987/development-and-characterization-of-a-human-and-mouse-intestinal-epithelial-cell-monolayer-platform
#5
Kenji Kozuka, Ying He, Samantha Koo-McCoy, Padmapriya Kumaraswamy, Baoming Nie, Karen Shaw, Priscilla Chan, Michael Leadbetter, Limin He, Jason G Lewis, Ziyang Zhong, Dominique Charmot, Marwan Balaa, Andrew J King, Jeremy S Caldwell, Matthew Siegel
We describe the development and characterization of a mouse and human epithelial cell monolayer platform of the small and large intestines, with a broad range of potential applications including the discovery and development of minimally systemic drug candidates. Culture conditions for each intestinal segment were optimized by correlating monolayer global gene expression with the corresponding tissue segment. The monolayers polarized, formed tight junctions, and contained a diversity of intestinal epithelial cell lineages...
November 7, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29153425/fluoroethoxy-1-4-diphenethylpiperidine-and-piperazine-derivatives-potent-and-selective-inhibitors-of-3-h-dopamine-uptake-at-the-vesicular-monoamine-transporter-2
#6
Emily R Hankosky, Shyam R Joolakanti, Justin R Nickell, Venumadhav Janganati, Linda P Dwoskin, Peter A Crooks
A small library of fluoroethoxy-1,4-diphenethyl piperidine and fluoroethoxy-1,4-diphenethyl piperazine derivatives were designed, synthesized and evaluated for their ability to inhibit [(3)H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and dopamine transporter (DAT), [(3)H]serotonin (5-HT) uptake at the serotonin transporter (SERT), and [(3)H]dofetilide binding at the human-ether-a-go-go-related gene (hERG) channel. The majority of the compounds exhibited potent inhibition of [(3)H]DA uptake at VMAT2, Ki changes in the nanomolar range (Ki = 0...
October 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29145140/fluoxetine-modulates-the-transcription-of-genes-involved-in-serotonin-dopamine-and-adrenergic-signalling-in-zebrafish-embryos
#7
V Cunha, P Rodrigues, M M Santos, P Moradas-Ferreira, M Ferreira
Neurotransmitters pathways in fish and mammals are phylogenetically conserved. Therefore, the environmental presence of psychopharmaceuticals, such as fluoxetine (FLU), are likely to interact with fish serotonergic, dopaminergic and adrenergic systems, affecting their response and associated biological functions. Hence, the present work aimed at evaluating the effects of FLU in the transcription of genes involved in serotonin, dopamine and adrenergic transporters and receptors signalling in early stages of Danio rerio development...
October 27, 2017: Chemosphere
https://www.readbyqxmd.com/read/29138116/in-silico-identification-of-genes-involved-in-chronic-metabolic-acidosis
#8
Ishfaq A Sheikh, Adeel Malik, Sameera F M AlBasri, Mohd A Beg
AIMS: Chronic metabolic acidosis (CMA) refers to increased plasma acidity due to disturbed acid-base equilibrium in human body. CMA leads to many dysfunctions including disorders of intestinal metabolism and barrier functions. The human body responds to these intestinal dysfunctions by creating a compensatory mechanism at genomic level in intestinal epithelial cells. This study was to identify the molecular pathways involved in metabolic dysfunction and compensatory adaptations in intestinal epithelium during CMA...
November 11, 2017: Life Sciences
https://www.readbyqxmd.com/read/29136336/effect-of-polymorphisms-on-the-pharmacokinetics-pharmacodynamics-and-safety-of-sertraline-in-healthy-volunteers
#9
Miriam Saiz-Rodríguez, Carmen Belmonte, Manuel Román, Dolores Ochoa, Dora Koller, María Talegón, María C Ovejero-Benito, Rosario López-Rodríguez, Teresa Cabaleiro, Francisco Abad-Santos
Sertraline is a selective serotonin reuptake inhibitor (SSRI) widely metabolized in the liver by cytochrome P450 (CYP) enzymes. Besides, it is a P-glycoprotein substrate. Moreover, serotonin transporters and serotonin receptors are involved in its efficacy and safety. The aim of the present study was to evaluate the role of polymorphisms of metabolizing enzymes, transporters and receptors on the pharmacokinetics, pharmacodynamics and tolerability of sertraline in healthy volunteers. Forty-six healthy volunteers (24 men and 22 women) receiving a 100-mg single oral dose of sertraline were genotyped for 17 genetic variants of CYP enzymes (CYP2B6, CYP2C9, CYP2C19, CYP2D6), ATP binding cassette subfamily B member 1 (ABCB1), Solute carrier family 6 member 4 (SLC6A4), 5-Hydroxytryptamine receptor 2A (HTR2A) and 5-Hydroxytryptamine receptor 2C (HTR2C) genes...
November 14, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29134560/neurochemical-and-neurotoxic-effects-of-mdma-ecstasy-and-caffeine-after-chronic-combined-administration-in-mice
#10
Anna Maria Górska, Katarzyna Kamińska, Agnieszka Wawrzczak-Bargieła, Giulia Costa, Micaela Morelli, Ryszard Przewłocki, Grzegorz Kreiner, Krystyna Gołembiowska
MDMA (3,4-methylenedioxymethamphetamine) is a psychostimulant popular as a recreational drug because of its effect on mood and social interactions. MDMA acts at dopamine (DA) transporter (DAT) and serotonin (5-HT) transporter (SERT) and is known to induce damage of dopamine and serotonin neurons. MDMA is often ingested with caffeine. Caffeine as a non-selective adenosine A1/A2A receptor antagonist affects dopaminergic and serotonergic transmissions. The aim of the present study was to determine the changes in DA and 5-HT release in the mouse striatum induced by MDMA and caffeine after their chronic administration...
November 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29131097/fluoxetine-treatment-in-rats-increases-the-rate-of-taurine-transport-in-mononuclear-cells
#11
María Gabriela Colmenares-Aguilar, Mary Urbina, Francisco Obregón, Fili Fazzino, Lucimey Lima
Fluoxetine, a selective serotonin reuptake inhibitor antidepressant, modulates the mitogen-induced proliferation of lymphocytes. Lymphocytes contain taurine and express taurine transporter (TauT). Among the effects of taurine on lymphocytes are protection against oxidants and regulation of the inflammatory aspects of the immune response. Our aim was to determine the influence of fluoxetine treatment on taurine transport, and to determine the presence of TauT in the mononuclear cells of rats. METHODS: Male adult Sprague-Dawley rats were treated with fluoxetine 10 mg/kg i...
November 1, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/29129791/resting-state-networks-mediate-the-effect-of-genotype-by-environment-interaction-on-mental-health
#12
Gennady G Knyazev, Alexander N Savostyanov, Andrey V Bocharov, Daria V Bazovkina, Ekaterina A Proshina
A number of studies have shown that the presence of short (S) allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with a higher risk for depression following exposure to stressful life events. These findings are in line with neuroimaging studies showing that 5-HTTLPR polymorphism has an effect on the connectivity among key areas involved in emotion regulation. Here using mediated moderation analysis, we show that electrophysiological manifestations of resting state networks in the alpha frequency band mediate the effect of 5-HTTLPR by stress interaction on depression/anxiety symptoms in a nonclinical sample...
November 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/29123483/impact-of-vortioxetine-on-synaptic-integration-in-prefrontal-subcortical-circuits-comparisons-with-escitalopram
#13
Shreaya Chakroborty, Thomas R Geisbush, Elena Dale, Alan L Pehrson, Connie Sánchez, Anthony R West
Prefrontal-subcortical circuits support executive functions which often become dysfunctional in psychiatric disorders. Vortioxetine is a multimodal antidepressant that is currently used in the clinic to treat major depressive disorder. Mechanisms of action of vortioxetine include serotonin (5-HT) transporter blockade, 5-HT1A receptor agonism, 5-HT1B receptor partial agonism, and 5-HT1D, 5-HT3, and 5-HT7 receptor antagonism. Vortioxetine facilitates 5-HT transmission in the medial prefrontal cortex (mPFC), however, the impact of this compound on related prefrontal-subcortical circuits is less clear...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29120604/molecular-determinants-for-substrate-interactions-with-the-glycine-transporter-glyt2
#14
Jane E Carland, Michael Thomas, Shannon N Mostyn, Nandhitha Subramanian, Megan Louise O'Mara, Renae M Ryan, Robert J Vandenberg
Transporters in the SLC6 family play key roles in regulating neurotransmission and are the targets for a wide range of therapeutics. Important insights into the transport mechanisms and the specificity of drug interactions of SLC6 transporters have been obtained from the crystal structures of a bacterial homolog of the family, LeuTAa, and more recently the Drosophila dopamine transporter and the human serotonin transporter. However, there is disputed evidence that the bacterial leucine transporter, LeuTAa, contains two substrate binding sites that work cooperatively in the mechanism of transport, with the binding of a second substrate being required for the release of the substrate from the primary site...
November 9, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29119704/pharmacokinetics-of-rp5063-following-single-doses-to-normal-healthy-volunteers-and-multiple-doses-over-10-days-to-stable-schizophrenic-patients
#15
Marc Cantillon, Robert Ings, Laxminarayan Bhat
RP5063, a multimodal dopamine (D)-serotonin (5-HT) stabilizer, possesses high affinity for D2/3/4 and 5-HT1A/2A/2B/2C/6/7 receptors and moderate affinity for the serotonin transporter. Two phase I studies characterized the pharmacokinetics of a single dose (10 and 15 mg fasting, 15 mg fed/fasting) in healthy volunteers and multiple doses (10, 20, 50, and 100 mg fed) over 10 days in patients with stable schizophrenia. RP5063 displayed a dose-dependent Cmax at 4 to 6 h, linear dose proportionality for both Cmax and AUC, and a half-life between 40 and 71 h...
November 8, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/29118341/novel-serotonin-transporter-regulators-natural-aristolane-and-nardosinane-types-of-sesquiterpenoids-from-nardostachys-chinensis-batal
#16
Ying-Peng Chen, Shu-Song Ying, Hong-Hong Zheng, Yan-Ting Liu, Zhong-Ping Wang, Hu Zhang, Xu Deng, Yi-Jing Wu, Xiu-Mei Gao, Tian-Xiang Li, Yan Zhu, Yan-Tong Xu, Hong-Hua Wu
Serotonin transporter (SERT) is a classic target of drug discovery for neuropsychiatric and digestive disorders, and against those disorders, plants of Nardostachys genus have been valued for centuries in the systems of Traditional Chinese Medicine, Ayurvedic and Unani. Herein, chemical investigation on the roots and rhizomes of Nardostachys chinensis Batal. led to the isolation of forty sesquiterpenoids including six new aristolane-type sesquiterpenoids and six new nardosinane-type sesquiterprenoids. Their structures were elucidated by extensive spectroscopic methods, combined with analyses of circular dichroism and single-crystal X-ray diffraction data...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117778/serotonin-a-mediator-of-the-gut-brain-axis-in-multiple-sclerosis
#17
Tsveta S Malinova, Christine D Dijkstra, Helga E de Vries
BACKGROUND: The significance of the gut microbiome for the pathogenesis of multiple sclerosis (MS) has been established, although the underlying signaling mechanisms of this interaction have not been sufficiently explored. OBJECTIVES: We address this point and use serotonin (5-hydroxytryptamine (5-HT))-a microbial-modulated neurotransmitter (NT) as a showcase to demonstrate that NTs regulated by the gut microbiome are potent candidates for mediators of the gut-brain axis in demyelinating disorders...
November 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29114103/association-of-serotonin-transporter-gene-alujb-methylation-with-major-depression-amygdala-responsiveness-5-httlpr-rs25531-polymorphism-and-stress
#18
Ilona Schneider, Harald Kugel, Ronny Redlich, Dominik Grotegerd, Christian Bürger, Paul-Christian Bürkner, Nils Opel, Katharina Dohm, Dario Zaremba, Susanne Meinert, Nina Schröder, Anna Milena Straßburg, Kathrin Schwarte, Christiane Schettler, Oliver Ambrée, Stephan Rust, Katharina Domschke, Volker Arolt, Walter Heindel, Bernhard T Baune, Weiqi Zhang, Udo Dannlowski, Christa Hohoff
DNA methylation profiles of the serotonin transporter gene (SLC6A4) have been shown to alter SLC6A4 expression, drive antidepressant treatment response and modify brain functions. This study investigated whether methylation of an AluJb element in the SLC6A4 promotor was associated with major depressive disorder (MDD), amygdala reactivity to emotional faces, 5-HTTLPR/rs25531 polymorphism, and recent stress. MDD patients (n=122) and healthy controls (HC, n=176) underwent fMRI during an emotional face-matching task...
November 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29104073/acute-effects-of-vortioxetine-and-duloxetine-on-resting-state-functional-connectivity-in-the-awake-rat
#19
Pablo D Pérez, Zhiwei Ma, Christina Hamilton, Connie Sánchez, Arne Mørk, Alan L Pehrson, Christoffer Bundgaard, Nanyin Zhang
The antidepressant vortioxetine exerts its effects via modulation of several serotonin (5-HT) receptors and inhibition of the 5-HT transporter (SERT). Additionally, vortioxetine has beneficial effects on aspects of cognitive dysfunction in depressed patients. However, a global examination of the drug effect on brain network connectivity is still missing. Here we compared the effects of vortioxetine and a serotonin norepinephrine reuptake inhibitor, duloxetine, on resting-state functional connectivity (RSFC) across the whole brain in awake rats using a combination of pharmacological and awake animal resting-state functional magnetic resonance imaging (rsfMRI) techniques...
November 2, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29102815/combining-genetic-and-epigenetic-parameters-of-the-serotonin-transporter-gene-in-obsessive-compulsive-disorder
#20
Edna Grünblatt, Zoya Marinova, Alexander Roth, Elena Gardini, Juliane Ball, Julia Geissler, Tomasz K Wojdacz, Marcel Romanos, Susanne Walitza
While genetic variants have been reported to be associated with obsessive-compulsive disorder (OCD), the small effect sizes suggest that epigenetic mechanisms such as DNA methylation may also be relevant. The serotonin transporter (SLC6A4) gene has been extensively investigated in relation to OCD, since serotonin reuptake inhibitors are the pharmacological treatment of choice for the disorder. The current study set three questions: Firstly, whether the high expressing loci of the SLC6A4 polymorphisms, 5-HTTLPR + rs25531, rs25532 and rs16965628 are associated with family-based (n = 164 trios) and case-control OCD (n = 186, 152, respectively)...
October 16, 2017: Journal of Psychiatric Research
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