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tryptophan hydroxylase

Adrian M Russo, Adam J Lawther, Benjamin M Prior, Luke Isbel, W Gregory Somers, John A Lesku, Amanda L Richdale, Cheryl Dissanayake, Stephen Kent, Christopher A Lowry, Matthew W Hale
Autism spectrum disorder (ASD) is a heterogeneous and highly heritable condition with multiple aetiologies. Although the biological mechanisms underlying ASD are not fully understood, evidence suggests that dysregulation of serotonergic systems play an important role in ASD psychopathology. Preclinical models using mice with altered serotonergic neurotransmission may provide insight into the role of serotonin in behaviours relevant to clinical features of ASD. For example, BALB/c mice carry a loss-of-function single nucleotide polymorphism (SNP; C1473 G) in tryptophan hydroxylase 2 (Tph2), which encodes the brain-specific isoform of the rate-limiting enzyme for serotonin synthesis, and these mice frequently have been used to model symptoms of ASD...
June 20, 2018: Behavioural Brain Research
Haijiao Wang, Wenqian Liu, Feng Shi, Lei Huang, Jiazhang Lian, Liang Qu, Jin Cai, Zhinan Xu
Cellular metabolic networks should be carefully balanced using metabolic engineering to produce the desired products at the industrial scale. As the precursor for the biosynthesis of the neurotransmitter serotonin, 5-hydroxytryptophan (5-HTP) is effective in treating a variety of diseases, such as depression, fibromyalgia, obesity, and cerebellar ataxia. Due to the lack of an efficient synthetic method, commercial production of 5-HTP is only achieved by extracting from the seeds of Griffonia Smplicifolia. This study reports efficient microbial production of 5-HTP via metabolically engineered Escherichia coli...
June 19, 2018: Metabolic Engineering
Katherine A Lyseng-Williamson
Telotristat ethyl (Xermelo® ), a first-in-class peripheral tryptophan hydroxylase (TPH) inhibitor, is approved to treat carcinoid syndrome diarrhoea in combination with somatostatin analogue (SSA) therapy in adults inadequately controlled by SSA therapy alone. Some neuroendocrine tumours secrete serotonin (5-HT) into the blood, resulting in frequent bowel movements (BMs) and other symptoms. Telotristat ethyl inhibits TPH, thereby reducing the production of 5-HT and improving carcinoid syndrome diarrhoea. In the 12-week placebo-controlled phase of randomized trials in patients with carcinoid syndrome diarrhoea (most of whom were receiving SSA therapy), the addition of oral telotristat ethyl 250 three times daily provided significant reductions in the frequency of BMs and levels of urinary 5-hydroxyindolacetic acid (u5-HIAA; a metabolite of 5-HT) relative to placebo...
June 2018: Drugs
Hui-Ai Zhang, Nan Sang, Xian Ge, Qian Huang, Xue-Liang Li, Jie Sha
Nesfatin-1, a satiety molecule processed from nucleobindin2 (NUCB2), is implicated in visceral hypersensitivity in rats and colocalized with 5-hydroxytryptamine (5-HT) in the dorsal raphe nucleus (DRN). Maternal separation (MS) in rats contributes to visceral hypersensitivity via elevated expression of 5-HT in the DRN. Intracerebroventricular injection of nesfatin-1 activates DRN 5-HT neurons. In this study, A model of visceral hypersensitivity was developed by subjecting rats to MS. Colorectal distension was used to detect visceral sensitivity, which was evaluated by abdominal withdrawal reflex (AWR) scores and electromyogram (EMG) magnitude...
June 19, 2018: Scientific Reports
Zulvikar Syambani Ulhaq, Mitsuyo Kishida
Teleost fish are known to express two isoforms of P450 aromatase, a key enzyme for estrogen synthesis. One of the isoforms, brain aromatase (AroB), cyp19a1b , is highly expressed during early development of zebrafish, thereby suggesting its role in brain development. On the other hand, early development of serotonergic neuron, one of the major monoamine neurons, is considered to play an important role in neurogenesis. Therefore, in this study, we investigated the role of AroB in development of serotonergic neuron by testing the effects of (1) estradiol (E2 ) exposure and (2) morpholino (MO)-mediated AroB knockdown...
2018: Frontiers in Endocrinology
Takeshi Chiba, Tomoji Maeda, Kenzo Kudo
 Intrinsic serotonin (5-hydroxytryptamine; 5-HT) synthesized within the mammary epithelium has an important physiological role in milk volume homeostasis in many species including mice, cows, and humans. During lactation, mammary epithelial cells activate 5-HT synthesis by tryptophan hydroxylase 1 (TPH1). TPH1 catalyzes the rate-limiting step in 5-HT biosynthesis within mammary glands. 5-HT synthesized in mammary glands is released into both the apical (milk) and basolateral spaces by a vesicular monoamine transporter...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Ryosuke Morinaga, Nobuaki Nakamuta, Yoshio Yamamoto
The ventral respiratory column (VRC) generates rhythmical respiration and is divided into four compartments: the Bötzinger complex (BC), pre-Bötzinger complex (PBC), rostral ventral respiratory group (rVRG), and caudal ventral respiratory group (cVRG). Serotonergic nerve fibers are densely distributed in the rostral to caudal VRC and serotonin would be one of the important modulators for the respiratory control in the VRC. In the present study, to elucidate detailed distribution of serotonergic neurons in raphe nuclei projecting to the various rostrocaudal levels of VRC, we performed combination of retrograde tracing technique by cholera toxin B subunit (CTB) with immunohistochemistry for tryptophan hydroxylase 2 (TPH2)...
May 24, 2018: Neuroscience Research
Paolo Giuffrida, Alessandro Vanoli, Elena Biletta, Catherine Klersy, Gaetano Bergamaschi, Gianluca M Sampietro, Sandro Ardizzone, Ombretta Luinetti, Michele Martino, Marco Vincenzo Lenti, Nicola Aronico, Marco Curti, Rachele Manca, Paolo Fociani, Marta Truffi, Fabio Corsi, Gino Roberto Corazza, Antonio Di Sabatino
BACKGROUND: Inflammatory bowel disease (IBD) is associated with neuroendocrine cell hyperplasia. AIMS: We investigated neuroendocrine cells in J-pouches of patients with ulcerative colitis undergoing restorative proctocolectomy and ileal pouch-anal anastomosis. METHODS: Sections from pouch biopsies of 17 patients and ileal biopsies of 17 active IBD patients and 16 controls were processed by immunohistochemistry for chromogranin A (CgA) and serotonin...
April 28, 2018: Digestive and Liver Disease
Dariusz Pawlak, Beata Znorko, Bartlomiej Kalaska, Tomasz Domaniewski, Radosław Zawadzki, Paweł Lipowicz, Michał Doroszko, Urszula Łebkowska, Piotr Grabowski, Krystyna Pawlak
LP533401 is an orally bioavailable small molecule that inhibits tryptophan hydroxylase-1, an enzyme responsible for the synthesis of gut-derived serotonin (GDS). Recently, we showed that increased GDS in rats with chronic kidney disease (CKD) affected bone strength and metabolism. We tested the hypothesis that treatment with LP533401 could reverse CKD-induced bone loss in uremia. Sixteen weeks after 5/6 nephrectomy, rats were randomized into untreated (CKD), treated with vehicle (VEH) and LP533401 at a dose of 30 or 100 mg/kg daily for 8 weeks...
May 21, 2018: Bone
Juan Díaz-Ramos, Maribel Flores-Flores, María E Ayala, Andrés Aragón-Martínez
Spermatogenesis and steroidogenesis are testicular functions regulated by gonadotrophins as well as other factors, including serotonin. Testicular serotonin acts as an autocrine regulator of testosterone secretion, but studies on its role in spermatogenesis and sperm quality are scarce. Here, we analyzed the effects of intratesticular inhibition of serotonin synthesis on gonadotrophins, testosterone, and sperm quality. Both testicles of 30-day-old rats were injected once with saline solution (SS) or distinct concentrations of p-chloroamphetamine (PCA) (0...
May 22, 2018: Systems Biology in Reproductive Medicine
Jimena Laura Frontera, Victoria María Gonzalez Pini, Fernando Luis Messore, Alicia Brusco
The endocannabinoid (eCB) system is involved in the modulation of the reward system and participates in the reinforcing effects of different drugs of abuse, including alcohol. The most abundant receptor of the eCB system in the central nervous system is the CB1 receptor (CB1R), which is predominantly expressed in areas involved in drug addiction, such as the nucleus accumbens, the ventral tegmental area, the substantia nigra and the raphe nucleus. CB1R is expressed in early stages during development, and reaches maximum levels during early adolescence...
May 16, 2018: Neuropharmacology
Koen Willem Ottenhof, Mari Sild, Mélissa Luce Lévesque, Henricus Gerardus Ruhé, Linda Booij
Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in brain serotonin synthesis. The TPH2 gene has frequently been investigated in relation to psychiatric morbidity. The aim of the present review is to integrate results from association studies between TPH2 single nucleotide polymorphisms (SNPs) and various psychiatric disorders, which we furthermore quantified with meta-analysis. We reviewed 166 studies investigating 69 TPH2 SNPs in a broad range of psychiatric disorders, including over 30,000 patients...
May 15, 2018: Neuroscience and Biobehavioral Reviews
Yusuke Obara, Takuji Machida, Yuho Takano, Saki Shiga, Asami Suzuki, Naoya Hamaue, Kenji Iizuka, Masahiko Hirafuji
We previously reported that cisplatin potentiated ileal 5-hydroxytryptamine (5-HT) metabolism and caused pathological changes with an inflammatory response in the delayed phase (72 h) after administration to rats. In the present study, we further investigated the time-dependent effect of cisplatin on ileal 5-HT metabolism and the effects of combining cisplatin and anti-inflammatory drugs on ileal tryptophan hydroxylase expression and pica (the consumption of non-nutritive materials such as kaolin). Cyclooxygenase-2 (COX-2) expression was significantly increased at 24 h after cisplatin (5 mg/kg, intraperitoneal) administration...
May 15, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Zhi-Gang He, Quan Wang, Run-Shan Xie, Yong-Sheng Li, Qing-Xiong Hong, Hong-Bing Xiang
To investigate autonomic substrates of brainstem-gut circuitry identified using trans-synaptic tracing with pseudorabies virus (PRV)-152, a strain that expresses enhanced green fluorescent protein, and PRV-614, a strain that expresses enhanced red fluorescent protein, injecting into the rat rectum wall. 3-7 days after PRV-152 injection, spinal cord and brainstem were removed and sectioned, and processed for PRV-152 visualization using immunofluorescence labeling against PRV-152. 6 days after PRV-614 injection, brainstem was sectioned and the neurochemical phenotype of PRV-614-positive neurons was identified using double immunocytochemical labeling against PRV-614 and TPH...
2018: American Journal of Clinical and Experimental Immunology
Stephanie Mandic, Hélène Volkoff
Monoamine neurotransmitters such as catecholamines [dopamine (DA), norepinephrine (NE) and epinephrine (E)] and serotonin have been shown to influence feeding in vertebrates. In order to better understand the role of monoamine neurotransmitters in the regulation of feeding in fish, we examined the effects of fasting on the brain and intestine gene expression of enzymes involved in their synthesis pathways (SPR: sepiapterin reductase; DHPR: dihydropteridine reductase; TH: tyrosine hydroxylase; TPH: tryptophan hydroxylase; AADC: aromatic l-amino acid decarboxylase; DBH: dopamine β-hydroxylase) in goldfish...
May 3, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Martin O Weickert, Gregory Kaltsas, Dieter Hörsch, Pablo Lapuerta, Marianne Pavel, Juan W Valle, Martyn E Caplin, Emily Bergsland, Pamela L Kunz, Lowell B Anthony, Enrique Grande, Kjell Öberg, Staffan Welin, Catherine Lombard-Bohas, John K Ramage, Ashwin Kittur, Qi M Yang, Matthew H Kulke
PURPOSE: In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4...
June 2018: Clinical Therapeutics
Xianwei Zhu, Zhibin Liu, Yifei Qin, Wenmin Niu, Qiang Wang, Lu Li, Jing Zhou
BACKGROUND: Treatment with electroacupuncture (EA) at ST25 and CV12 has a significant analgesic effect on postinflammatory irritable bowel syndrome (PI-IBS) visceral pain. Enterochromaffin (EC) cells and serotonin (5-hydroxytryptamine (5-HT)) are important in the development of visceral hyperalgesia. OBJECTIVE: To investigate the analgesic effect and underlying mechanisms of EA at ST25 and CV12 on the treatment of trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS visceral hyperalgesia in rats...
May 2, 2018: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
Sunmi Song, Christopher Steven Marcum, Anna V Wilkinson, Sanjay Shete, Laura M Koehly
Background: Despite prevalent binge drinking and alcohol-dependent symptoms among Hispanics, few studies have examined how multidimensional factors influence Hispanic adolescents' binge drinking. Purpose This study examines the effects of genetic, psychological, and social network factors on binge drinking over time among Mexican heritage adolescents in the USA and whether there are correlations among genetic variants that are associated with binge drinking and psychological and network characteristics...
April 24, 2018: Annals of Behavioral Medicine: a Publication of the Society of Behavioral Medicine
Rachel A Ungar, Neelam Giri, Maryland Pao, Payal P Khincha, Weiyin Zhou, Blanche P Alter, Sharon A Savage
Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome caused by germline mutations in telomere biology genes. Patients have extremely short telomeres for their age and a complex phenotype including oral leukoplakia, abnormal skin pigmentation, and dysplastic nails in addition to bone marrow failure, pulmonary fibrosis, stenosis of the esophagus, lacrimal ducts and urethra, developmental anomalies, and high risk of cancer. We evaluated a patient with features of DC, mood dysregulation, diabetes, and lack of pubertal development...
June 2018: American Journal of Medical Genetics. Part A
A S Tsybko, T V Ilchibaeva, D V Bazovkina, V S Naumenko
The effects of chronic 5-HT1A receptor activation on the behavior, functional activity of 5-HT1A receptors, and expression of key genes of the brain 5-HT system were studied in mice of the catalepsy-prone CBA strain and the catalepsy-resistant C57BL/6 strain. Chronic treatment with 8-Hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) (1.0 mg/kg i.p., 14 days) led to a significant decrease in the hypothermic response to acute administration of 8-OH-DPAT in CBA and C57BL/6 mice, which indicates the desensiti-zation of 5-HT1A receptors in both strains...
March 2018: Molekuliarnaia Biologiia
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