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Serotonin transporter

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https://www.readbyqxmd.com/read/27918771/association-of-selective-serotonin-reuptake-inhibitors-with-the-risk-for-spontaneous-intracranial-hemorrhage
#1
Christel Renoux, Sarah Vahey, Sophie Dell'Aniello, Jean-François Boivin
Importance: Selective serotonin reuptake inhibitors (SSRIs) may increase the risk for spontaneous intracranial hemorrhage (ICH), an effect that is in theory linked to the strength of inhibition of serotonin reuptake of an antidepressant. However, whether antidepressants that are strong inhibitors of serotonin reuptake actually increase the risk for ICH and the effect of concomitant use of antithrombotics are unknown. Objectives: To assess the risk for ICH associated with the use of SSRIs compared with tricyclic antidepressants (TCAs) among new users of antidepressants and according to the relative affinity of the antidepressant for the serotonin transporter and to assess whether concomitant use of antithrombotics modifies this risk...
December 5, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27916355/enhanced-serotonin-signaling-increases-intestinal-neuroplasticity
#2
Chasen J Greig, Neeru Gandotra, John J Tackett, Michaela C Bamdad, Robert A Cowles
BACKGROUND: The intestinal mucosa recovers from injury by accelerating enterocyte proliferation resulting in villus growth. A similar phenomenon is seen after massive bowel resection. Serotonin (5-HT) has been implicated as an important regulator of mucosal homeostasis by promoting growth in the epithelium. The impact of 5-HT on other components of growing villi is not known. We hypothesized that 5-HT-stimulated growth in the intestinal epithelium would be associated with growth in other components of the villus such as enteric neural axonal processes...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27909858/distribution-and-morphology-of-cholinergic-cells-in-the-branchial-epithelium-of-zebrafish-danio-rerio
#3
Peter C Zachar, Wen Pan, Michael G Jonz
Acetylcholine is an excitatory neurotransmitter important for oxygen sensing in mammals. A cholinergic mechanism in the fish gill has been implicated in the hyperventilatory response to acute hypoxia; however, the identity and distribution of acetylcholine-containing cells in the gills is poorly defined. We test the hypothesis that cholinergic cells are present in the gill filament epithelium in zebrafish (Danio rerio), a model vertebrate for which oxygen chemoreceptors are well characterized, and that these cells would receive nervous innervation...
December 2, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27909009/association-of-protein-distribution-and-gene-expression-revealed-by-pet-and-post-mortem-quantification-in-the-serotonergic-system-of-the-human-brain
#4
A Komorowski, G M James, C Philippe, G Gryglewski, A Bauer, M Hienert, M Spies, A Kautzky, T Vanicek, A Hahn, T Traub-Weidinger, D Winkler, W Wadsak, M Mitterhauser, M Hacker, S Kasper, R Lanzenberger
Regional differences in posttranscriptional mechanisms may influence in vivo protein densities. The association of positron emission tomography (PET) imaging data from 112 healthy controls and gene expression values from the Allen Human Brain Atlas, based on post-mortem brains, was investigated for key serotonergic proteins. PET binding values and gene expression intensities were correlated for the main inhibitory (5-HT1A) and excitatory (5-HT2A) serotonin receptor, the serotonin transporter (SERT) as well as monoamine oxidase-A (MAO-A), using Spearman's correlation coefficients (rs) in a voxel-wise and region-wise analysis...
November 30, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27907003/mapping-cholesterol-interaction-sites-on-serotonin-transporter-through-coarse-grained-molecular-dynamics
#5
Mariarosaria Ferraro, Matteo Masetti, Maurizio Recanatini, Andrea Cavalli, Giovanni Bottegoni
Serotonin transporter (SERT) modulates serotonergic signaling via re-uptake of serotonin in pre-synaptic cells. The inclusion in cholesterol-enriched membrane domains is crucial for SERT activity, suggesting a cross-talk between the protein and the sterol. Here, we develop a protocol to identify potential cholesterol interaction sites coupling statistical analysis to multi-microsecond coarse-grained molecular dynamics simulations of SERT in a previously validated raft-like membrane model. Six putative sites were found, including a putative CRAC motif on TM4 and a CARC motif on TM10...
2016: PloS One
https://www.readbyqxmd.com/read/27906640/a-review-of-the-implication-of-hypoxanthine-excess-in-the-physiopathology-of-lesch-nyhan-disease
#6
R J Torres, C Prior, M G Garcia, J G Puig
Lesch-Nyhan disease is caused by HGprt deficiency, however, the mechanism by which enzyme deficiency leads to the severe neurological manifestations is still unknown. We hypothesized that hypoxanthine excess leads, directly or indirectly, through its action in adenosine transport, to aberrations in neuronal development. We found that hypoxanthine diminishes adenosine transport and enhances stimulation of adenosine receptors. These effects cause an imbalance between adenosine, dopamine, and serotonin receptors in HGprt deficient cells, and cells differentiated with hypoxanthine showed an increase in dopamine, adenosine and serotonin receptors expression...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27891211/from-linked-open-data-to-molecular-interaction-studying-selectivity-trends-for-ligands-of-the-human-serotonin-and-dopamine-transporter
#7
Barbara Zdrazil, Eva Hellsberg, Michael Viereck, Gerhard F Ecker
Retrieval of congeneric and consistent SAR data sets for protein targets of interest is still a laborious task to do if no appropriate in-house data set is available. However, combining integrated open data sources (such as the Open PHACTS Discovery Platform) with workflow tools now offers the possibility of querying across multiple domains and tailoring the search to the given research question. Starting from two phylogenetically related protein targets of interest (the human serotonin and dopamine transporters), the whole chemical compound space was explored by implementing a scaffold-based clustering of compounds possessing biological measurements for both targets...
September 14, 2016: MedChemComm
https://www.readbyqxmd.com/read/27890559/fluoxetine-and-its-active-metabolite-norfluoxetine-disrupt-estrogen-synthesis-in-a-co-culture-model-of-the-feto-placental-unit
#8
Andrée-Anne Hudon Thibeault, Laetitia Laurent, Sung Vo Duy, Sébastien Sauvé, Patrick Caron, Chantal Guillemette, J Thomas Sanderson, Cathy Vaillancourt
The effects of fluoxetine, one of the most prescribed selective serotonin-reuptake inhibitors (SSRIs) during pregnancy, and its active metabolite norfluoxetine were studied on placental aromatase (CYP19) and feto-placental steroidogenesis Fluoxetine did not alter estrogen secretion in co-culture of fetal-like adrenocortical (H295R) and trophoblast-like (BeWo) cells used as a model of the feto-placental unit, although it induced CYP19 activity, apparently mediated by the serotonin (5-HT) 2A receptor/PKC signalling pathway...
November 24, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27889580/methylphenidate-modulates-dorsal-raphe-neuronal-activity-behavioral-and-neuronal-recordings-from-adolescent-rats
#9
Holly Whitt, Natasha Kharas, Nachum Dafny, Cruz Reyes-Vasquez
Methylphenidate (MPD) is a widely prescribed psychostimulants used for the treatment of attention deficit hyperactive disorder (ADHD). Unlike the psychostimulants cocaine and amphetamine, MPD does not exhibit direct actions on the serotonin transporter, however there is evidence suggesting that the therapeutic effects of MPD may be mediated in part by alterations in serotonin transmission. This study aimed to investigate the role of the dorsal raphe (DR) nucleus, one of the major sources of serotonergic innervation in the mammalian brain, in the response to MPD exposure...
November 23, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27888722/a-pilot-study-on-predictors-of-brainstem-raphe-abnormality-in-patients-with-major-depressive-disorder
#10
Milutin Kostić, Ana Munjiza, Danilo Pesic, Amir Peljto, Ivana Novakovic, Valerija Dobricic, Dusica Lecic Tosevski, Milija Mijajlovic
BACKGROUND: Hypo/anechogenicity of the brainstem raphe (BR) structures has been suggested as a possible transcranial parenchymal sonography (TCS) marker associated with depression. AIM: The aim of this study was to analyze possible association of the abnormal BR echogenicity in patients with major depression when compared to healthy controls, and to evaluate its clinical and genetic correlates. METHODS: TCS was performed in 53 patients diagnosed as major depressive disorder (MDD) without psychotic symptoms and in 54 healthy matched controls...
November 22, 2016: Journal of Affective Disorders
https://www.readbyqxmd.com/read/27882537/neurochemical-and-behavioral-effects-of-hypidone-hydrochloride-yl-0919-a-novel-combined-selective-serotonin-reuptake-inhibitor-and-partial-5-ht1a-agonist
#11
Li-Ming Zhang, Xiao-Yun Wang, Nan Zhao, Yu-Lu Wang, Xiao-Xu Hu, Yu-Hua Ran, Yan-Qin Liu, You-Zhi Zhang, Ri-Fang Yang, Yun-Feng Li
The purpose of the present study was to investigate the pharmacology of hypidone hydrochloride (YL-0919), a novel selective serotonin reuptake inhibitor (SSRI) and 5-hydroxytryptamine (5-HT)1A receptor agonist with high affinity for serotonin transporter (SERT) and 5-HT1A receptors. YL-0919 promoted [(35) S]GTPγ S binding at 85% of the magnitude of the full 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), suggesting that YL-0919 is a high-efficacy partial agonist of 5-HT1A receptors...
November 24, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27880876/an-integrative-review-of-methylation-at-the-serotonin-transporter-gene-and-its-dialogue-with-environmental-risk-factors-psychopathology-and-5-httlpr
#12
REVIEW
H Palma-Gudiel, L Fañanás
Gene-environment (GxE) interactions have largely been regarded as the root of many complex disorders, including several psychiatric disorders. In this regard, it has been hypothesized that epigenetic mechanisms may be the main mediators of such interactions. Of particular interest is the previously described interaction between psychosocial stress and genetic variability of the serotonin transporter gene (SLC6A4) in its polymorphic region 5-HTTLPR. Here we review the literature concerning SLC6A4 methylation in association with environmental, clinical or genetic variables...
November 20, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27869229/tetratricopeptide-repeat-domain-9a-modulates-anxiety-like-behavior-in-female-mice
#13
Lee Wei Lim, Smeeta Shrestha, Yu Zuan Or, Shawn Zheng Kai Tan, Hwa Hwa Chung, Yang Sun, Chew Leng Lim, Sharafuddin Khairuddin, Thomas Lufkin, Valerie Chun Ling Lin
Tetratricopeptide repeat domain 9A (TTC9A) expression is abundantly expressed in the brain. Previous studies in TTC9A knockout (TTC9A(-/-)) mice have indicated that TTC9A negatively regulates the action of estrogen. In this study we investigated the role of TTC9A on anxiety-like behavior through its functional interaction with estrogen using the TTC9A(-/-) mice model. A battery of tests on anxiety-related behaviors was conducted. Our results demonstrated that TTC9A(-/-) mice exhibited an increase in anxiety-like behaviors compared to the wild type TTC9A(+/+) mice...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27866207/post-stroke-fatigue-may-be-associated-with-the-promoter-region-of-a-monoamine-oxidase-a-gene-polymorphism
#14
Smi Choi-Kwon, Mihye Ko, Sang-Eun Jun, Juhan Kim, Kyung-Hee Cho, Hyun-Wook Nah, Hasup Song, Jong S Kim
BACKGROUND: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. METHODS: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A)...
November 19, 2016: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/27865645/discovery-of-smp-304-a-novel-benzylpiperidine-derivative-with-serotonin-transporter-inhibitory-activity-and-5-ht1a-weak-partial-agonistic-activity-showing-the-antidepressant-like-effect
#15
Hidefumi Yoshinaga, Shuji Masumoto, Koji Koyama, Naoya Kinomura, Yuji Matsumoto, Taro Kato, Satoko Baba, Kenji Matsumoto, Tomoko Horisawa, Hitomi Oki, Kazuki Yabuuchi, Toru Kodo
We report the discovery of a novel benzylpiperidine derivative with serotonin transporter (SERT) inhibitory activity and 5-HT1A receptor weak partial agonistic activity showing the antidepressant-like effect. The 3-methoxyphenyl group and the phenethyl group of compound 1, which has weak SERT binding activity, but potent 5-HT1A binding activity, were optimized, leading to compound 35 with potent and balanced dual SERT and 5-HT1A binding activity, but also potent CYP2D6 inhibitory activity. Replacement of the methoxy group in the left part of compound 35 with a larger alkoxy group, such as ethoxy, isopropoxy or methoxy-ethoxy group ameliorated CYP2D6 inhibition, giving SMP-304 as a candidate...
October 29, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27861613/non-serotonergic-neurotoxicity-by-mdma-ecstasy-in-neurons-derived-from-mouse-p19-embryonal-carcinoma-cells
#16
Dina Popova, Andréas Forsblad, Sanaz Hashemian, Stig O P Jacobsson
3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays...
2016: PloS One
https://www.readbyqxmd.com/read/27860344/combined-simulation-and-mutation-studies-to-elucidate-selectivity-of-unsubstituted-amphetamine-like-cathinones-at-the-dopamine-transporter
#17
Amir Seddik, Daan P Geerke, Thomas Stockner, Marion Holy, Oliver Kudlacek, Nicholas V Cozzi, Arnold E Ruoho, Harald H Sitte, Gerhard F Ecker
The dopamine and serotonin transporter proteins (DAT, SERT) play a vital role in behavior and mental illness. Although their substrate transport has been studied extensively, the molecular basis of their selectivity is not completely understood yet. In this study, we exploit molecular dynamics simulations combined with mutagenesis studies to shed light on the driving factors for DAT-over-SERT selectivity of a set of cathinones. Results indicate that these compounds can adopt two binding modes of which one is more favorable...
November 8, 2016: Molecular Informatics
https://www.readbyqxmd.com/read/27856786/a-high-resolution-in-vivo-atlas-of-the-human-brain-s-serotonin-system
#18
Vincent Beliveau, Melanie Ganz, Ling Feng, Brice Ozenne, Liselotte Højgaard, Patrick M Fisher, Claus Svarer, Douglas N Greve, Gitte M Knudsen
: The serotonin (5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. We here present a high-resolution multi-dimensional in vivo atlas of four of the human brain's 5-HT receptors (5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4) as well as of the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) scans, acquired in a total of 210 healthy individuals...
November 17, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27856628/analysis-of-extrastriatal-123i-fp-cit-binding-contributes-to-the-differential-diagnosis-of-parkinsonian-diseases
#19
Merijn Joling, Chris Vriend, Odile A Van den Heuvel, Pieter G H M Raijmakers, Paul A Jones, Henk W Berendse, Jan Booij
: (123)I-FP-CIT SPECT can visualise and quantify striatal dopamine transporter (DAT) binding in vivo. In addition, (123)I-FP-CIT has modest affinity for the serotonin transporter (SERT), predominantly represented in extrastriatal binding. Based on previous imaging studies that have suggested more pronounced degeneration of other monoaminergic systems in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) than in Parkinson's disease (PD), we hypothesised that, in addition to striatal DAT binding, there would be differences in extrastriatal (123)I-FP-CIT SPECT binding to SERT between MSA, PSP and PD...
November 17, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27836486/immunochemical-localization-of-vesicular-monoamine-transporter-2-vmat2-in-mouse-brain
#20
Rachel A Cliburn, Amy R Dunn, Kristen A Stout, Carlie A Hoffman, Kelly M Lohr, Alison I Bernstein, Emily J Winokur, James Burkett, Yvonne Shmitz, William M Caudle, Gary W Miller
Vesicular monoamine transporter 2 (VMAT2, SLC18A2) is a transmembrane transporter protein that packages dopamine, serotonin, norepinephrine, and histamine into vesicles in preparation for neurotransmitter release from the presynaptic neuron. VMAT2 function and related vesicle dynamics have been linked to susceptibility to oxidative stress, exogenous toxicants, and Parkinson's disease. To address a recent depletion of commonly used antibodies to VMAT2, we generated and characterized a novel rabbit polyclonal antibody generated against a 19 amino acid epitope corresponding to an antigenic sequence within the C-terminal tail of mouse VMAT2...
November 8, 2016: Journal of Chemical Neuroanatomy
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