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https://www.readbyqxmd.com/read/29223399/ectopic-serotonin-production-in-%C3%AE-cell-specific-transgenic-mice
#1
Hyeongseok Kim, Hyunki Kim, Kyuho Kim, Michael S German, Hail Kim
Genetically modified mice have been widely used in the field of β-cell research. However, analysis of results gathered using genetically modified organisms should be interpreted carefully as the results may be confounded by several factors. Here, we showed the ectopic serotonin (5-HT) production in β-cells of RIP-CreMgn, MIP-GFP, and MIP-Cre/ERT. These mice contained a human growth hormone (hGH) cassette to enhance transgene expression and hGH expression and Stat5 phosphorylation were detected in pancreatic islets of these mice...
December 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29194046/updates-on-the-biology-of-serotonin-and-tryptophan-hydroxylase
#2
Tara Swami, H Christian Weber
PURPOSE OF REVIEW: To summarize the most recent findings relevant to the biology of serotonin (5-hydroxytryptamine; 5-HT) and the enzyme tryptophan hydroxylase (TPH) in human gastrointestinal disease. RECENT FINDINGS: Serotonin is synthesized in the central nervous system (CNS) and the gastrointestinal tract where it is secreted from enteroendocrine cells. Its biosynthesis is regulated by two isoforms of the enzyme TPH of which TPH1 is localized predominantly in gastrointestinal enteroendocrine cells...
November 30, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/29133842/serotonin-regulates-prostate-growth-through-androgen-receptor-modulation
#3
Emanuel Carvalho-Dias, Alice Miranda, Olga Martinho, Paulo Mota, Ângela Costa, Cristina Nogueira-Silva, Rute S Moura, Natalia Alenina, Michael Bader, Riccardo Autorino, Estêvão Lima, Jorge Correia-Pinto
Aging and testosterone almost inexorably cause benign prostatic hyperplasia (BPH) in Human males. However, etiology of BPH is largely unknown. Serotonin (5-HT) is produced by neuroendocrine prostatic cells and presents in high concentration in normal prostatic transition zone, but its function in prostate physiology is unknown. Previous evidence demonstrated that neuroendocrine cells and 5-HT are decreased in BPH compared to normal prostate. Here, we show that 5-HT is a strong negative regulator of prostate growth...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29123193/characterization-of-mammary-specific-disruptions-for-tph1-and-lrp5-during-murine-lactation
#4
Samantha R Weaver, Nicholas J Jury, Karen A Gregerson, Nelson D Horseman, Laura L Hernandez
Serotonin is a homeostatic regulator of the mammary gland during lactation. The contribution of mammary-derived serotonin to circulating serum serotonin concentrations was previously unknown. We have developed mice with mammary-specific disruptions of tryptophan hydroxylase 1 (Tph1) or low-density lipoprotein receptor-related protein 5 (Lrp5) that are induced during late pregnancy and lactation via use of the whey acidic protein (WAP)-Cre cre-lox system. Our objective was to characterize dams with a lactation- and mammary-specific disruption of Lrp5 (WAP-Cre × Lrp5 (FL/FL)) or Tph1 (WAP-Cre × Tph1 (FL/FL))...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122693/vitamin-a-improves-the-symptoms-of-autism-spectrum-disorders-and-decreases-5-hydroxytryptamine-5-ht-a-pilot-study
#5
Min Guo, Jiang Zhu, Ting Yang, Xi Lai, Xiao Liu, Juan Liu, Jie Chen, Tingyu Li
Autism spectrum disorders (ASD) are complicated neurodevelopmental disorders. Many studies have demonstrated that children with autism have multiple nutritional deficiencies and increased serum 5-hydroxytryptamine (5-HT) levels. In our previous study, 77.9% of autistic children were found to have vitamin A deficiency, and the concentration of vitamin A was negatively associated with the CARS score. In the present study, we sought to test whether vitamin A supplementation could improve autistic symptoms and decrease serum 5-HT levels...
November 6, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29035515/isoform-specific-substrate-inhibition-mechanism-of-human-tryptophan-hydroxylase
#6
Kasper D Tidemand, Günther H Peters, Pernille Harris, Eva Stensgaard, Hans E M Christensen
Tryptophan hydroxylase (TPH) catalyzes the initial and rate-limiting step in the biosynthesis of serotonin, which is associated with a variety of disorders such as depression and irritable bowel syndrome. TPH exists in two isoforms: TPH1 and TPH2. TPH1 catalyzes the initial step in the synthesis of serotonin in the peripheral tissues, while TPH2 catalyzes this step in the brain. In this study, the steady-state kinetic mechanism for the catalytic domain of human TPH1 has been determined. Varying substrate tryptophan (Trp) and tetrahydrobiopterin (BH4) results in a hybrid Ping Pong-ordered mechanism in which the reaction can either occur through a Ping Pong or a sequential mechanism depending on the concentration of tryptophan...
October 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/29031728/single-cell-rna-sequencing-reveals-a-distinct-population-of-proglucagon-expressing-cells-specific-to-the-mouse-upper-small-intestine
#7
Leslie L Glass, Fernando J Calero-Nieto, Wajid Jawaid, Pierre Larraufie, Richard G Kay, Berthold Göttgens, Frank Reimann, Fiona M Gribble
OBJECTIVES: To identify sub-populations of intestinal preproglucagon-expressing (PPG) cells producing Glucagon-like Peptide-1, and their associated expression profiles of sensory receptors, thereby enabling the discovery of therapeutic strategies that target these cell populations for the treatment of diabetes and obesity. METHODS: We performed single cell RNA sequencing of PPG-cells purified by flow cytometry from the upper small intestine of 3 GLU-Venus mice. Cells from 2 mice were sequenced at low depth, and from the third mouse at high depth...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28991991/effects-of-ghrelin-on-nocturnal-melatonin-secretion-in-sheep-an-in-vitro-and-in-vivo-approach
#8
K Kirsz, M Szczesna, E Molik, D A Zieba
Recent studies confirmed that pineal melatonin (MEL) secretion is regulated by ghrelin (GHRL) in seasonally reproductive sheep. The first in vivo experiment investigated whether the effect of GHRL on nocturnal secretion of MEL in sheep is mediated by type 2 serotonin receptors. Sheep ( = 16) were intravenously injected with GHRL (2.5 μg/kg of BW) and meta-Chlorophenylpiperazine (mCPP; a mixed agonist of 5-HT2B/5-HT2C receptors; 1 mg/kg BW), either combined or individually, during the short-day (SDS) and long-day (LDS) seasons...
September 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28968985/stress-inhibits-tryptophan-hydroxylase-expression-in-a-rat-model-of-depression
#9
Yi Chen, Haixia Xu, Mingyue Zhu, Kun Liu, Bo Lin, Ruxian Luo, Chuanbai Chen, Mengsen Li
Serotonin (5-hydroxytryptamine, 5-HT) dysfunction is associated with the pathophysiology of depression. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, is believed to have essential role in many mental disorders, including depression. In the present study, we generated a rat model of depression by exposing the animals to stress, and the rats were then treated with paroxetine. The results indicated that the concentration of 5-HT in the brain and liver tissues were significantly lower in the rat model of depression than in healthy or treated rats...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28951738/serotonin-related-gene-variants-in-patients-with-irritable-bowel-syndrome-and-depressive-or-anxiety-disorders
#10
Magdalena Grzesiak, Jan Aleksander Beszłej, Ewa Waszczuk, Marcin Szechiński, Monika Szewczuk-Bogusławska, Dorota Frydecka, Tadeusz Dobosz, Anna Jonkisz, Arleta Lebioda, Małgorzata Małodobra, Agata Mulak
AIM: To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS). METHODS: The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria. SCL6A4 HTTLPR polymorphism (rs4795541) was determined using PCR-based method...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28948742/-effects-of-baldrinal-of-valeriana-jatamansi-on-expression-of-crf-tph1-mrna-and-5-ht-in-rats-with-irritable-bowel-syndrome
#11
Si-Yu Tao, Cong-Rui Xiao, Jing Wang, Shu-Jing Zhang, Yu-Shan Gao, Fang-Yuan Mu, Yi-Cheng Wang, Xing-Li Yan
This study aimed to investigate the effects of baldrinal of Valeriana jatamansi on the expression of corticotropin releasing factor (CRF) and tryptophan hydroxylase 1 (TPH1) mRNA and levels of 5-hydroxytryptamine (5-HT) in colon of rats with irritable bowel syndrome (IBS), and to explain its therapeutic mechanism on IBS through 5-HT pathway. Fifty-four male SD rats were randomly divided into 6 groups: blank group, model group, baldrinal high, medium and low dose groups, and pinaverium bromide group, n=9 in each group...
January 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28902619/a-case-control-association-study-of-12-candidate-genes-and-attempted-suicide-in-french-adolescents
#12
Bojan Mirkovic, David Cohen, Claudine Laurent, Malaika Lasfar, Christophe Marguet, Prsicille Gerardin
Background Suicide is the second leading cause of death for 10-19-year-olds. Evidence has shown that attempted suicide is a complex interplay of genes and environmental factors. In the adult population, possible associations between genetic polymorphisms and suicidal behaviors have been investigated for several genes, most often with inconsistent findings and poor replicability of significant associations. This study aimed to identify gene variants conferring risk for adolescent suicide attempt. Methods We selected the genes and variants after an analysis of the literature and a selection of the most significant associations identified...
September 13, 2017: International Journal of Adolescent Medicine and Health
https://www.readbyqxmd.com/read/28855642/peripheral-serotonin-regulates-postoperative-intra-abdominal-adhesion-formation-in-mice
#13
Jianbin Bi, Simin Zhang, Zhaoqing Du, Jia Zhang, Yan Deng, Chang Liu, Jingyao Zhang
The aim of the present study is to investigate the role and potential mechanisms of peripheral serotonin in postoperative intra-abdominal adhesion formation in mice. The caecum-rubbing operations were conducted for intra-abdominal adhesion formation modelling in wild-type and Tph1-/- mice. The deficiency of serotonin significantly decreased the adhesion scores, weight loss, and adhesion thickness as well as levels of collagen fibres and hydroxyproline in the adhesive tissues. The Tph1-/- mice exhibited a milder inflammatory response and oxidative stress in the adhesive tissues than did the wild-type mice...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794173/glucose-potentiates-%C3%AE-cell-function-by-inducing-tph1-expression-in-rat-islets
#14
Yuqing Zhang, Ruyuan Deng, Xue Yang, Wan Xu, Yun Liu, Fengying Li, Juan Zhang, Hongju Tang, Xueying Ji, Yufang Bi, Xiao Wang, Libin Zhou, Guang Ning
Impaired pancreatic β-cell function is the primary defect in type 2 diabetes. Glucose is an important regulator of β-cell growth and function; however, the mechanisms that are involved in the chronic adaptation of β-cells to hyperglycemia remain largely unknown. In the present study, global gene expression patterns revealed that tryptophan hydroxylase 1 (Tph1) was the most profound of genes that are up-regulated in rat islets exposed to high glucose. Calcium and cAMP signals synergistically mediated glucose-stimulated Tph1 transcription in β-cells by activating cAMP-responsive element-binding protein and promoting its binding with a Tph1 promoter...
August 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28774871/enteric-serotonin-and-oxytocin-endogenous-regulation-of-severity-in-a-murine-model-of-necrotizing-enterocolitis
#15
Kara Gross Margolis, Jennifer Vittorio, Maria Talavera, Karen Gluck, Zhishan Li, Alina Iuga, Korey Stevanovic, Virginia Saurman, Narek Israelyan, Martha G Welch, Michael D Gershon
Necrotizing enterocolitis (NEC), a gastrointestinal inflammatory disease of unknown etiology, causes a great deal of morbidity and mortality in premature infants. The liver as well as the gut may be affected in NEC. We tested the hypothesis that signaling molecules, which are endogenous to the bowel, regulate the severity of experimental NEC in mice. Specifically, we postulated that mucosal serotonin (5-HT), which is proinflammatory, would increase the severity of NEC and that oxytocin (OT), which is present in enteric neurons and is anti-inflammatory, would oppose NEC...
August 3, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28751862/utp-gated-signaling-pathways-of-5-ht-release-from-bon-cells-as-a-model-of-human-enterochromaffin-cells
#16
Andromeda Liñán-Rico, Fernando Ochoa-Cortes, Alix Zuleta-Alarcon, Mazin Alhaj, Esmerina Tili, Josh Enneking, Alan Harzman, Iveta Grants, Sergio Bergese, Fievos L Christofi
Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to trigger or modulate gut neural reflexes and transmit information about visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms modulating Ca(2+)-dependent 5-HT release are not understood. Previous studies indicated that purinergic signaling via ATP and ADP is an important mechanism in modulation of 5-HT release. However, EC cells also respond to UTP and UDP suggesting uridine triphosphate receptor and signaling pathways are involved as well...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28751217/human-placenta-expresses-both-peripheral-and-neuronal-isoform-of-tryptophan-hydroxylase
#17
Laetitia Laurent, Kathy Deroy, Joey St-Pierre, Francine Côté, J Thomas Sanderson, Cathy Vaillancourt
The role of placental serotonin has been an active topic of research notably because of its crucial role in brain development. However, which cell types synthesize serotonin in human placenta remains unknown. Moreover, it is not known if the two tryptophan hydroxylase isoforms (TPH1 and TPH2), the rate-limiting enzymes in serotonin biosynthesis, are expressed in placenta. Human placentas were obtained in first trimester or at term, and trophoblast cells were isolated and purified using a magnetic cell sorter and placed in primary culture...
September 2017: Biochimie
https://www.readbyqxmd.com/read/28719094/discovery-and-characterization-of-a-novel-tryptophan-hydroxylase-1-inhibitor-as-a-prodrug
#18
Hailong Shi, Yaya Cui, Yifei Qin
Serotonin (5-HT) is an important neurotransmitter and paracrine signaling molecule in the gastrointestinal tract. Two distinct tryptophan hydroxylases (TPH), TPH1 and TPH2 are the rate-limiting enzymes in the 5-HT biosynthesis process. TPH1 expression is mainly limited in the enterochromaffin cells and distributed in peripheries such as the skin and gut, while TPH2 is the predominant isoform in the CNS. In this study, mol002291 was screened as a drug-like compound from the TCM database for the inhibitor of TPH...
July 18, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28716530/genetic-association-analysis-of-serotonin-and-signal-transduction-pathways-in-suicide-attempters-from-an-italian-sample-of-psychiatric-patients
#19
Maurizio Pompili, Giovanna Gentile, Catia Scassellati, Cristian Bonvicini, Marco Innamorati, Denise Erbuto, Franco Montebovi, Giuseppe Ducci, Alberto Forte, Eleonora De Pisa, Stefano Ferracuti, Gianluca Serafini, Vincenzo De Luca, Mario Amore, Maurizio Simmaco, Paolo Girardi
Genetic factors have been reported to contribute to the liability of suicide. We aimed to investigate functional polymorphisms in eight genes (serotonin transporter, SLC6A4; receptors, 5HTR1A, 1B, 5HTR2A; Tryptophan Hydroxylase, TPH1, TPH2; Monoamine Oxidase, MAOA and G Protein Subunit Beta 3, GNB3) to investigate their predictive value for suicide. The possible confounding effects of gender and phenotypic patients dissection were also valued. A sample of 111 consecutive psychiatric inpatients was recruited and assessed using specific psychometric instruments...
July 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28706142/stress-inhibits-tryptophan-hydroxylase-expression-in-a-rat-model-of-depression
#20
Yi Chen, Haixia Xu, Mingyue Zhu, Kun Liu, Bo Lin, Ruxian Luo, Chuanbai Chen, Mengsen Li
Serotonin (5-hydroxytryptamine, 5-HT) dysfunction is associated with the pathophysiology of depression. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, is believed to have essential role in many mental disorders, including depression. In the present study, we generated a rat model of depression by exposing the animals to stress, and the rats were then treated with paroxetine. The results indicated that the concentration of 5-HT in the brain and liver tissues were significantly lower in the rat model of depression than in healthy or treated rats...
June 28, 2017: Oncotarget
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