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Serotonin transporter

Alexander V Kulikov, Raul R Gainetdinov, Evgeni Ponimaskin, Allan V Kalueff, Vladimir S Naumenko, Nina K Popova
Selective serotonin reuptake inhibitors (SSRIs) are the most effective and most used antidepressant drugs. Acting by inhibiting serotonin (5-HT) transporter, SSRIs display a typical 3-4-week delay in their therapeutic effects, with nearly 40% of depressed patients remaining treatment-resistant. Recent evidence suggests complex interplay between 5-HT receptors and key proteins of 5-HT metabolism in molecular mechanisms of such delay and resistance to SSRIs. Area covered: This paper concentrates on the interplay between 5-HT receptors in the delay of therapeutic effect of SSRIs, and the interaction between tryptophan hydroxylase 2 and 5-HT transporter in the SSRI resistance...
March 15, 2018: Expert Opinion on Therapeutic Targets
Marenka Smit, David Vállez García, Bauke M de Jong, Evelien Zoons, Jan Booij, Rudi A Dierckx, Antoon T Willemsen, Erik F de Vries, Anna L Bartels, Marina A Tijssen
Purpose: Alterations of the central serotonergic system have been implicated in the pathophysiology of dystonia. In this molecular imaging study, we assessed whether altered presynaptic serotonin transporter (SERT) binding contributes to the pathophysiology of cervical dystonia (CD), concerning both motor and non-motor symptoms (NMS). Methods: We assessed the non-displaceable binding potential (BPND ) using the selective SERT tracer [11 C]DASB and positron emission tomography (PET) in 14 CD patients and 12 age- and gender-matched controls...
2018: Frontiers in Neurology
Asghar M Razavi, George Khelashvili, Harel Weinstein
BACKGROUND: Much of the structure-based mechanistic understandings of the function of SLC6A neurotransmitter transporters emerged from the study of their bacterial LeuT-fold homologs. It has become evident, however, that structural differences such as the long N- and C-termini of the eukaryotic neurotransmitter transporters are involved in an expanded set of functional properties to the eukaryotic transporters. These functional properties are not shared by the bacterial homologs, which lack the structural elements that appeared later in evolution...
March 14, 2018: BMC Biology
D A Nikishin, N M Alyoshina, Y B Shmukler
Using RT-PCR, we showed the presence of Tph1 mRNA in follicular cells and Tph2 mRNA in oocytes isolated from primary multilayer ovarian follicles of mouse and the absence of Ddc expression, which indicates that serotonin cannot be synthesized in a developing ovarian follicle. The membrane serotonin transporter Sert is expressed in follicular cells and oocytes. Experiments on the cultivation of follicles in vitro confirmed the absence of serotonin synthesis from 5-hydroxytryptophan and the presence of membrane transport activity in the oocyte...
January 2018: Doklady. Biochemistry and Biophysics
Yong-Ku Kim, Byung-Joo Ham, Kyu-Man Han
The etiology of depression is characterized by the interplay of genetic and environmental factors and brain structural alteration. Childhood adversity is a major contributing factor in the development of depression. Interactions between childhood adversity and candidate genes for depression could affect brain morphology via the modulation of neurotrophic factors, serotonergic neurotransmission, or the hypothalamus-pituitary-adrenal (HPA) axis, and this pathway may explain the subsequent onset of depression...
March 10, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
E M Peter-Ross
The pathobiological causes, the shared cellular and molecular pathways in catatonia and in catatonic presentation in neuropsychiatric disorders are yet to be determined. The hypotheses in this paper have been deduced from the latest scientific research findings and clinical observations of patients with genetic disorders, behavioral phenotypes and other family members suffering mental disorders. The first hypothesis postulates that catatonia and the heterogeneity of catatonic signs and symptoms involve nucleolar dysfunction arising from abnormalities of the brain-specific, non-coding micro-RNA, SNORD115 genes (either duplications or deletions) which result in pathobiological dysfunction of various combinations in the downstream pathways (possibly along with other genes in these shared pathways)...
April 2018: Medical Hypotheses
Stefano Cinque, Francesca Zoratto, Anna Poleggi, Damiana Leo, Luca Cerniglia, Silvia Cimino, Renata Tambelli, Enrico Alleva, Raul R Gainetdinov, Giovanni Laviola, Walter Adriani
Alterations in dopamine neurotransmission are generally associated with diseases such as attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Such diseases typically feature poor decision making and lack of control on executive functions and have been studied through the years using many animal models. Dopamine transporter (DAT) knockout (KO) and heterozygous (HET) mice, in particular, have been widely used to study ADHD. Recently, a strain of DAT KO rats has been developed (1)...
2018: Frontiers in Psychiatry
Angela D'Ascola, Giuseppe Bruschetta, Gabriella Zanghì, Salvatore Campo, Pietro Medica, Stefania Campana, Guido Ferlazzo, Bernhard F Gibbs, Alida Maria Ferlazzo
Serotonin (5-HT) is a neurohormone transported from plasma into platelets and leukocytes by a specific transporter (SERT). While it is known that the brain 5-HT system is modulated by physical exercise, the peripheral serotoninergic response to exercise is not yet fully elucidated. In particular, this study aimed to evaluate changes in plasma 5-HT levels and equine leukocyte SERT expression in response to treadmill exercise in untrained horses. Analyses were carried out pre- and post-treadmill exercise. 5-HT plasma levels were analysed by HPLC...
February 27, 2018: Research in Veterinary Science
Lianwei Mu, Dong Dong Xia, Teresa Michalkiewicz, Matthew Hodges, Gary Mouradian, Girija G Konduri, Margaret T T Wong-Riley
We have identified a critical period of respiratory development in rats at postnatal days P12-13, when inhibitory influence dominates and when the response to hypoxia is at its weakest. This critical period has significant implications for Sudden Infant Death Syndrome (SIDS), the cause of which remains elusive. One of the known risk factors for SIDS is prematurity. A common intervention used in premature infants is hyperoxic therapy, which, if prolonged, can alter the ventilatory response to hypoxia and induce sustained inhibition of lung alveolar growth and pulmonary remodeling...
March 2018: Physiological Reports
Julien Volle, Tatiana Bregman, Brian Scott, Mustansir Diwan, Roger Raymond, Paul J Fletcher, José N Nobrega, Clement Hamani
Both selective serotonin reuptake inhibitors (SSRIs) and ventromedial prefrontal cortex (vmPFC) deep brain stimulation (DBS) modulate serotonergic activity. We compared the acute (1 day) and long-term (12 days) effects of vmPFC stimulation and fluoxetine on serotonin (5-HT) release and receptor expression in rats. Samples to measure serotonin levels were collected from the hippocampus using microdialysis. Serotonin transporter (SERT), 5-HT1A and 5-HT1B mRNA were measured using in situ hybridization. [3 H]8-OH-DPAT and [125 I]cyanopindolol autoradiography were used to measure 5-HT1A and 5-HT1B binding...
March 2, 2018: Neuropharmacology
Patrick Neiens, Angela De Simone, Anna Ramershoven, Georg Höfner, Lars Allmendinger, Klaus T Wanner
MS Binding Assays represent a label free alternative to radioligand binding assays. In this study, we present an LC-ESI-MS/MS method for the quantification of (R,R)-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-ol ((R,R)-D-84, (R,R)-1), (S,S)-reboxetine ((S,S)-2), and (S)-citalopram ((S)-3) employed as highly selective nonlabelled reporter ligands in MS Binding Assays addressing the dopamine (DAT, (R,R)-D-84), the norepinephrine (NET, (S,S)-reboxetine), and the serotonin transporter (SERT, (S)-citalopram), respectively...
March 3, 2018: Biomedical Chromatography: BMC
Sheela Verjee, Anna Weston, Christiane Kolb, Heba Kalbhenn-Aziz, Veronika Butterweck
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis plays an important part in the development of depressive symptoms. In this study, the effects of a commercial St. John's wort extract (STW3-VI), hyperforin, miquelianin, and the selective serotonin reuptake inhibitor citalopram on the expression of genes relevant to HPA axis function were investigated in human neuronal cells. SH-SY5Y cells were treated with STW3-VI (20 µg/mL), hyperforin (1 µM), miquelianin (10 µM), or citalopram (10 µM) in the presence of the glucocorticoid receptor agonist dexamethasone (DEX,10 µM) for 6 h and 48 h, respectively...
March 2, 2018: Planta Medica
Landon M Klein, Nicholas V Cozzi, Paul F Daley, Simon D Brandt, Adam L Halberstadt
Substantial effort has been devoted toward understanding the psychopharmacological effects of tryptamine hallucinogens, which are thought to be mediated by activation of 5-HT2A and 5-HT1A receptors. Recently, several psychoactive tryptamines based on the N,N-diallyltryptamine (DALT) scaffold have been encountered as recreational drugs. Despite the apparent widespread use of DALT derivatives in humans, little is known about their pharmacological properties. We compared the binding affinities of DALT and its 2-phenyl-, 4-acetoxy-, 4-hydroxy-, 5-methoxy-, 5-methoxy-2-methyl-, 5-fluoro-, 5-fluoro-2-methyl-, 5-bromo-, and 7-ethyl-derivatives at 45 receptor and transporter binding sites...
February 27, 2018: Neuropharmacology
Farwa Sajadi, Carmela Curcuruto, Afra Al Dhaheri, Jean-Paul V Paluzzi
The mosquito, Aedes aegypti , is a vector responsible for transmitting various pathogens to humans, and their prominence as chief vectors of human disease is largely due to their anthropophilic blood feeding behaviour. Larval stage mosquitoes must deal with the potential dilution of their haemolymph in fresh water, whereas the haematophagus A. aegypti female faces the challenge of excess ion and water intake after a blood meal. The excretory system, comprised of the Malpighian tubules (MTs) and hindgut, is strictly controlled by neuroendocrine factors, responsible for the control of diuresis across all developmental stages...
March 1, 2018: Journal of Experimental Biology
Molly H B Amador, M Danielle McDonald
The serotonin transporter (SERT) functions in the uptake of the neurotransmitter serotonin (5-HT) from the extracellular milieu and is the molecular target of the selective serotonin reuptake inhibitors (SSRIs), a common group of antidepressants. The current study comprehensively assesses the sequence, tissue distribution, transport kinetics, and physiological function of a teleost SERT. The 2,022-bp toadfish SERT sequence encodes a protein of 673 amino acids, which shows 83% similarity to zebrafish SERT and groups with SERT of other teleosts in phylogenetic analysis...
February 27, 2018: Journal of Experimental Biology
Qiang Lu, Suguru Komenoi, Takako Usuki, Daisuke Takahashi, Fumio Sakane
We previously reported that brain-specific diacylglycerol kinase (DGK) δ-knockout (KO) mice showed obsessive-compulsive disorder (OCD)-like behaviors, which were alleviated by a serotonin (5-HT) transporter (SERT) inhibitor. However, the molecular mechanisms causing the OCD-like abnormal behaviors remain unclear. In the present study, we found that DGKδ deficiency increased SERT protein levels in the mouse cerebral cortex. Moreover, DGKδ interacted and co-localized with SERT. Furthermore, DGKδ-KO decreased tryptophan hydroxylase-2 expression and increased monoamine oxidase-A expression...
February 24, 2018: Biochemical and Biophysical Research Communications
Lars Farde, Pontus Plavén-Sigray, Jacqueline Borg, Simon Cervenka
Positron emission tomography has, for 30 years, been used in numerous case-control studies searching for hypothesized differences in the density of neuroreceptor or transporter proteins in psychiatric disorders such as schizophrenia and depression. In most cases, the results have not been conclusive. One reason could be the sizeable interindividual variability in biochemical markers, which in twin studies have shown to emanate from both environmental and genetic factors, leading to low statistical power for the detection of group effects...
April 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Limei Zhang, Vito S Hernández, Jerome D Swinny, Anil K Verma, Torsten Giesecke, Andrew C Emery, Kerim Mutig, Luis M Garcia-Segura, Lee E Eiden
The lateral habenula (LHb) has a key role in integrating a variety of neural circuits associated with reward and aversive behaviors. There is limited information about how the different cell types and neuronal circuits within the LHb coordinate physiological and motivational states. Here, we report a cell type in the medial division of the LHb (LHbM) in male rats that is distinguished by: (1) a molecular signature for GABAergic neurotransmission (Slc32a1/VGAT) and estrogen receptor (Esr1/ERα) expression, at both mRNA and protein levels, as well as the mRNA for vesicular glutamate transporter Slc17a6/VGLUT2, which we term the GABAergic estrogen-receptive neuron (GERN); (2) its axonal projection patterns, identified by in vivo juxtacellular labeling, to both local LHb and to midbrain modulatory systems; and (3) its somatic expression of receptors for vasopressin, serotonin and dopamine, and mRNA for orexin receptor 2...
February 26, 2018: Translational Psychiatry
Harvey G Roweth, Ruoling Yan, Nader H Bedwani, Alisha Chauhan, Nicole Fowler, Alice H Watson, Jean-Daniel Malcor, Stewart O Sage, Gavin E Jarvis
Citalopram prevents serotonin (5-HT) uptake into platelets by blocking the serotonin reuptake transporter (SERT). Although some clinical data suggest that selective serotonin reuptake inhibitors (SSRIs) may affect haemostasis and thrombosis, these poorly-characterised effects are not well understood mechanistically and useful in vitro data is limited. We sought to determine whether the inhibitory effects of citalopram on platelets are mediated via its pharmacological inhibition of 5-HT transport. We quantified the inhibitory potency of (RS)-, (R)- and (S)-citalopram on platelet function...
February 22, 2018: Scientific Reports
Margaret Mandy R MacLean
Increased synthesis of serotonin and/or activity of serotonin in pulmonary arteries has been implicated in the pathobiology of pulmonary arterial hypertension (PAH). The incidence of PAH associated with diet pills such as aminorex, fenfluramine, and chlorphentermine initially led to the "serotonin hypothesis of pulmonary hypertension." Over the last couple of decades there has been an accumulation of convincing evidence that targeting serotonin synthesis or signaling is a novel and promising approach to the development of novel therapies for PAH...
April 2018: Pulmonary Circulation
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