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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
Yong-Ku Kim, Meysam Amidfar, Eunsoo Won
The heterogeneity of post-traumatic stress disorder (PTSD) symptoms indicates that multiple neurobiological mechanisms underlie the pathophysiology of the condition. However, no generally accepted PTSD biomarkers in clinical practice currently exist. The sequential responses to recurrent and chronic stress by the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) system are considered to play a significant role in the onset and progression of PTSD. Decreased activity of the HPA axis and parasympathetic nervous system, along with increased activity of the sympathetic nervous system, have been observed in PTSD, which may lead to increased levels of proinflammatory cytokines...
June 19, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Austin L Hensley, Adam R Colley, Ashley Elizabeth Ross
Melatonin is an important hormone whose functions span from regulating circadian rhythm in the brain to providing anti-inflammatory properties in the immune system. Melatonin secretion from the pineal gland is known; however, the mechanism of melatonin signaling in the immune system is not well understood. The lymph node is the hub of the immune system and melatonin secretion from lymphocytes was proposed to be an important source specifically for regulating cytokine secretion. Methods exist to quantify the concentration of melatonin within biological samples; however, they often suffer from either a lack of selectivity for melatonin over common biological interferences or temporal resolution which is not amenable to measuring real-time signaling dynamics...
June 22, 2018: Analytical Chemistry
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
Sunyoung Park, Hyera Ryu, Ji-Yoon Lee, Aruem Choi, Dai-Jin Kim, Sung Nyun Kim, Jung-Seok Choi
Aims: The present study investigated neural connectivity associated with treatment responses in patients with Internet gaming disorder (IGD) using resting-state electroencephalography (EEG) coherence analyses. Methods: We included 30 patients with IGD and 32 healthy control subjects (HCs). Of the IGD patients, 18 completed an outpatient treatment that included pharmacotherapy with selective serotonin reuptake inhibitors for 6 months. Resting-state EEG coherence and self-report questionnaires were used to evaluate clinical and psychological features pre- and post-treatment, and data were analyzed using generalized estimating equations...
2018: Frontiers in Psychiatry
Andrea Porzionato, Elena Stocco, Diego Guidolin, Luigi Agnati, Veronica Macchi, Raffaele De Caro
In the carotid body (CB), a wide series of neurotransmitters and neuromodulators have been identified. They are mainly produced and released by type I cells and act on many different ionotropic and metabotropic receptors located in afferent nerve fibers, type I and II cells. Most metabotropic receptors are G protein-coupled receptors (GPCRs). In other transfected or native cells, GPCRs have been demonstrated to establish physical receptor-receptor interactions (RRIs) with formation of homo/hetero-complexes (dimers or receptor mosaics) in a dynamic monomer/oligomer equilibrium...
2018: Frontiers in Physiology
Saïd M'Dahoma, Matthieu Poitevin, Eric Dabala, Hugo Payan, Cecilia Gabriel, Elisabeth Mocaër, Sylvie Bourgoin, Michel Hamon
Previous data showed that neuropathic pain induced by mechanical lesion of peripheral nerves has specific characteristics and responds differently to alleviating drugs at cephalic versus extracephalic level. This is especially true for tricyclic antidepressants currently used for alleviating neuropathic pain in humans which are less effective against cephalic neuropathic pain. Whether this also applies to the antidepressant agomelatine, with its unique pharmacological properties as MT1 /MT2 melatonin receptor agonist and 5-HT2B /5-HT2C serotonin receptor antagonist, has been investigated in two rat models of neuropathic pain...
2018: Frontiers in Pharmacology
Steven T Laing, David Merriam, Barbara C Shock, Sarah Mills, Abbie Spinner, Rachel Reader, Dennis J Hartigan-O'Connor
Idiopathic chronic diarrhea (ICD) is a common ailment affecting captive rhesus macaques ( Macaca mulatta). ICD cases are characterized by diarrhea in the absence of commonly identified diarrheal pathogens and multiple recurrences even after supportive therapy. Histologically, the disease is characterized by lymphoplasmacytic colitis. We identified 35 rhesus macaques euthanized for ICD during a 7-month period and described demographic, clinical, histologic, and immunologic commonalities. We found a trend of historic Campylobacter spp...
January 1, 2018: Veterinary Pathology
Relish Shah, Emmanuelle Courtiol, Francisco X Castellanos, Catia M Teixeira
Serotonin (5-HT) is one of the best-studied modulatory neurotransmitters with ubiquitous presynaptic release and postsynaptic reception. 5-HT has been implicated in a wide variety of brain functions, ranging from autonomic regulation, sensory perception, feeding and motor function to emotional regulation and cognition. The role of this neuromodulator in neuropsychiatric diseases is unquestionable with important neuropsychiatric medications, e.g., most antidepressants, targeting this system. Importantly, 5-HT modulates neurodevelopment and changes in its levels during development can have life-long consequences...
2018: Frontiers in Behavioral Neuroscience
David Q Beversdorf, Allen L Carpenter, Jessica K Alexander, Neil T Jenkins, Michael R Tilley, Catherine A White, Ashleigh J Hillier, Ryan M Smith, Howard H Gu
BACKGROUND AND OBJECTIVE: Previous research has shown an effect of various psychosocial stressors on unconstrained cognitive flexibility, such as searching through a large set of potential solutions in the lexical-semantic network during verbal problem-solving. Functional magnetic resonance imaging has shown that the presence of the short (S) allele (lacking a 43-base pair repeat) of the promoter region of the gene (SLC6A4) encoding the serotonin transporter (5-HTT) protein is associated with a greater amygdalar response to emotional stimuli and a greater response to stressors...
June 2018: Cognitive and Behavioral Neurology: Official Journal of the Society for Behavioral and Cognitive Neurology
Petr Popov, Yao Peng, Ling Shen, Raymond C Stevens, Vadim Cherezov, Zhi-Jie Liu, Vsevolod Katritch
Engineering of GPCR constructs with improved thermostability is a key for successful structural and biochemical studies of this transmembrane protein family, targeted by 40% of all therapeutic drugs. Here we introduce a comprehensive computational approach to effective prediction of stabilizing mutations in GPCRs, named CompoMug, which employs sequence-based analysis, structural information, and a derived machine learning predictor. Tested experimentally on the serotonin 5-HT2C receptor target, CompoMug predictions resulted in 10 new stabilizing mutations, with an apparent thermostability gain ~8...
June 21, 2018: ELife
Shuang Li, Wen-Qing Yao, Ye-Zheng Tao, Lan Ma, Xing Liu
Serotonin (5-hydroxtryptamine, 5-HT), one of the central neurotransmitters, is the most important modulator for emotion regulation, sensory processing, cognitive control, etc. The serotonergic neurons are limited in amount and mainly distributed in the dorsal raphe nucleus (DR) and the median raphe nucleus (MR) in the midline of the brain stem. Previous studies mainly focused on the function of 5-HT neurons in the DR, but little is known about 5-HT neurons in MR. In the present study, with Pet1-Cre transgenic mice and DREADDs technology, we specifically activated or silenced 5-HT neurons in the MR, and aimed to explore their roles in anxiety- and depressive-like behaviors...
June 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Javier García-Nafría, Rony Nehmé, Patricia C Edwards, Christopher G Tate
G-protein-coupled receptors (GPCRs) form the largest family of receptors encoded by the human genome (around 800 genes). They transduce signals by coupling to a small number of heterotrimeric G proteins (16 genes encoding different α-subunits). Each human cell contains several GPCRs and G proteins. The structural determinants of coupling of Gs to four different GPCRs have been elucidated1-4 , but the molecular details of how the other G-protein classes couple to GPCRs are unknown. Here we present the cryo-electron microscopy structure of the serotonin 5-HT1B receptor (5-HT1B R) bound to the agonist donitriptan and coupled to an engineered Go heterotrimer...
June 20, 2018: Nature
Jesus E Madrid, Tara M Mandalaywala, Sean P Coyne, Jamie Ahloy-Dallaire, Joseph P Garner, Christina S Barr, Dario Maestripieri, Karen J Parker
Research has increasingly highlighted the role that developmental plasticity-the ability of a particular genotype to produce variable phenotypes in response to different early environments-plays as an adaptive mechanism. One of the most widely studied genetic contributors to developmental plasticity in humans and rhesus macaques is a serotonin transporter gene-linked polymorphic region (5-HTTLPR), which determines transcriptional efficiency of the serotonin transporter gene in vitro and modifies the availability of synaptic serotonin in these species...
June 27, 2018: Proceedings. Biological Sciences
L A Paes, O H Della Torre, T B Henriques, M P de Mello, E H R V Celeri, P Dalgalarrondo, G Guerra Júnior, A Dos Santos Júnior
Serotonin 2C receptors (5HT2C) are involved in serotonin-driven dynamic equilibrium adjustments responsible for homeostatic stability in brain structures that modulate behavior and emotions. Single nucleotide polymorphisms (SNPs) from the serotonin 2C receptor gene (HTR2C) have been associated with several neurological and mental disorders, including abnormalities in cognitive and emotional processes. The aim of this study was to evaluate the association between the rs6318 SNP of the HTR2C gene and behavioral characteristics exhibited by children and adolescents based on the Child Behavior Checklist (CBCL/6-18) inventory...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Hozumi Kumagai, Hitoshi Kusaba, Takeharu Yamanaka, Kenta Nio, Kyoko Inadomi, Kotoe Takayoshi, Mamoru Ito, Shingo Tamura, Akitaka Makiyama, Chinatsu Makiyama, Gen Hirano, Yoshihiro Shibata, Tsuyoshi Shirakawa, Kenji Mitsugi, Hiroshi Ariyama, Taito Esaki, Koichi Akashi, Eishi Baba
PURPOSE: Combination therapy of fosaprepitant, dexamethasone (DEX) and a serotonin (5-HT3) receptor antagonist is a standard antiemetic prophylaxis for patients receiving highly emetogenic chemotherapy (HEC). However, the appropriate dose of DEX has not been established in Japan. This study determined the efficacy and safety of triplet antiemetic prophylaxis in Japanese patients receiving HEC when administered the same doses of DEX as those given in a previous international phase 3 study on this drug...
June 2018: Medicine (Baltimore)
Mario Gennaro Mazza, Aurora Rossetti, Eugenia Rossana Botti, Massimo Clerici
RATIONALE: Vortioxetine is a new multimodal antidepressant approved by the Food and Drug Administration for the treatment of Major Depressive Disorder and recently introduced in Europe. While antidepressant properties of vortioxetine and its tolerability have been demonstrated by preclinical and clinical studies data on the safety of vortioxetine after overdose are still lacking. PATIENT CONCERNS: A 50-year-old Caucasian man presenting a severe depressive episode that in a suicide attempt he took vortioxetine at 250 mg...
June 2018: Medicine (Baltimore)
Jacob E Montgomery, Sarah Wahlstrom-Helgren, Timothy D Wiggin, Brittany M Corwin, Christina Lillesaar, Mark A Masino
Serotonin (5HT) is a modulator of many vital processes in the spinal cord (SC), such as production of locomotion. In the larval zebrafish, intraspinal serotonergic neurons (ISNs) are a source of spinal 5HT that, despite the availability of numerous genetic and optical tools, has not yet been directly shown to affect the spinal locomotor network. In order to better understand the functions of ISNs, we used a combination of strategies to investigate ISN development, morphology, and function. ISNs were optically isolated from one another by photoconverting Kaede fluorescent protein in individual cells, permitting morphometric analysis as they developed in vivo...
June 19, 2018: Developmental Neurobiology
I P Butkevich, V A Mikhailenko
We studied the effect of chronic injections of serotonin reuptake inhibitor fluoxetine to rats during pregnancy on physiological and behavioral characteristics of female offspring during the prepubertal period. Fluoxetine reduced body weight in newborn females, but this parameter was restored to normal values by the age of 25 days. Fluoxetine also increased animal anxiety, but did not change the level of depressive behavior and cognitive capacities. It was shown that chronic injections of physiological solution to pregnant female enhanced nociceptive responses in the offspring during the prepubertal period, while fluoxetine neutralized the consequences of invasive intervention, which was expressed in a lower level of pain reaction in the offspring...
June 19, 2018: Bulletin of Experimental Biology and Medicine
Huan Song, Fang Fang, Gunnar Tomasson, Filip K Arnberg, David Mataix-Cols, Lorena Fernández de la Cruz, Catarina Almqvist, Katja Fall, Unnur A Valdimarsdóttir
Importance: Psychiatric reactions to life stressors are common in the general population and may result in immune dysfunction. Whether such reactions contribute to the risk of autoimmune disease remains unclear. Objective: To determine whether there is an association between stress-related disorders and subsequent autoimmune disease. Design, Setting, and Participants: Population- and sibling-matched retrospective cohort study conducted in Sweden from January 1, 1981, to December 31, 2013...
June 19, 2018: JAMA: the Journal of the American Medical Association
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