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https://www.readbyqxmd.com/read/28719094/discovery-and-characterization-of-a-novel-tryptophan-hydroxylase-1-inhibitor-as-a-prodrug
#1
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/28719042/serotonergic-paraneurons-in-the-female-mouse-urethral-epithelium-and-their-potential-role-in-peripheral-sensory-information-processing
#2
F Aura Kullmann, Huiyi H Chang, Christian Gauthier, Bronagh M McDonnell, Jih-Chao Yeh, Dennis R Clayton, Anthony J Kanai, William C de Groat, Gerard L Apodaca, Lori A Birder
AIM: The mechanisms underlying detection and transmission of sensory signals arising from visceral organs, such as the urethra, are poorly understood. Recently, specialized ACh-expressing cells embedded in the urethral epithelium have been proposed as chemosensory sentinels for detection of bacterial infection. Here we examined the morphology and potential role in sensory signaling of a different class of specialized cells that express serotonin (5-HT), termed paraneurons. METHODS: Urethrae, dorsal root ganglia neurons and spinal cords were isolated from adult female mice and used for immunohistochemistry and calcium imaging...
July 18, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28714607/new-insights-into-how-serotonin-selective-reuptake-inhibitors-shape-the-developing-brain
#3
REVIEW
Jay A Gingrich, Heli Malm, Mark S Ansorge, Alan Brown, Andre Sourander, Deepika Suri, Cátia M Teixeira, Martha K Caffrey Cagliostro, Darshini Mahadevia, Myrna M Weissman
Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system (CNS) development, such sensitive periods shape the formation of neuro-circuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint, as well as the environmental context. While allowing for adaptation, such sensitive periods are also windows of vulnerability during which external and internal factors can confer risk to brain disorders by derailing adaptive developmental programs...
July 17, 2017: Birth defects research
https://www.readbyqxmd.com/read/28714029/involvement-of-gut-microbiota-in-the-association-between-gastrointestinal-motility-and-5%C3%A2-ht-expression-m2-macrophage-abundance-in-the-gastrointestinal-tract
#4
Mo Yang, Hirokazu Fukui, Hirotsugu Eda, Yoshitaka Kitayama, Ken Hara, Mio Kodani, Toshihiko Tomita, Tadayuki Oshima, Jiro Watari, Hiroto Miwa
Serotonin (5‑hydroxytryptamine; 5‑HT) may be a key player in gastrointestinal (GI) motility and the GI immune system. In the present study, the effect of gut microbiota on the association between GI motility, and 5‑HT expression and macrophage abundance in the GI tract was examined. Germ‑free (GF) mice (6 weeks old) were orally administered a fecal bacterial suspension prepared from specific pathogen‑free mice and their GI tissues were evaluated 4 weeks later. The expression of 5‑HT and mannose receptor (MR) was examined by immunohistochemistry, and GI transit time (GITT) was measured by administration of carmine red solution...
July 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713247/divergent-roles-of-central-serotonin-in-adult-hippocampal-neurogenesis
#5
REVIEW
Ning-Ning Song, Ying Huang, Xin Yu, Bing Lang, Yu-Qiang Ding, Lei Zhang
The central serotonin (5-HT) system is the main target of selective serotonin reuptake inhibitors (SSRIs), the first-line antidepressants widely used in current general practice. One of the prominent features of chronic SSRI treatment in rodents is the enhanced adult neurogenesis in the hippocampus, which has been proposed to contribute to antidepressant effects. Therefore, tremendous effort has been made to decipher how central 5-HT regulates adult hippocampal neurogenesis. In this paper, we review how changes in the central serotonergic system alter adult hippocampal neurogenesis...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28712263/effects-of-colostrum-serum-on-the-serotonergic-system-in-the-dorsal-raphe-nuclei-of-exercised-rats
#6
Tae-Woon Kim, Chang-Ju Kim, Jinhee Seo
PURPOSE: The central fatigue hypothesis suggests that exhaustion, or the maximum level of exercise, induces excessive stress and increases serotonin concentrations in the brain, which in turn decreases central nervous system (CNS) function and induces fatigue. Our aim was to determine the effects of colostrum serum on the serotonergic system in the dorsal raphe nuclei during exhaustive exercise. METHODS: Animals were randomly divided into five groups: control, exercise, exercise and treatment with 50, 100, and 200 mg/kg of colostrum serum...
March 31, 2017: Journal of Exercise Nutrition & Biochemistry
https://www.readbyqxmd.com/read/28711736/two-dose-investigation-of-the-5-ht-agonist-psilocybin-on-relative-and-global-cerebral-blood-flow
#7
Candace R Lewis, Katrin H Preller, Rainer Kraehenmann, Lars Michels, Philipp Stämpfli, Franz X Vollenweider
Psilocybin, the active compound in psychedelic mushrooms, is an agonist of various serotonin receptors. Seminal psilocybin positron emission tomography (PET) research suggested regional increases in glucose metabolism in frontal cortex (hyperfrontality). However, a recent arterial spin labeling (ASL) study suggests psilocybin may lead to hypo-perfusion in various brain regions. In this placebo-controlled, double-blind study we used pseudo-continuous ASL (pCASL) to measure perfusion changes, with and without adjustment for global brain perfusion, after two doses of oral psilocybin (low dose: 0...
July 12, 2017: NeuroImage
https://www.readbyqxmd.com/read/28711602/contribution-of-5-ht2a-receptors-on-diaphragmatic-recovery-after-chronic-cervical-spinal-cord-injury
#8
Kun-Ze Lee, Elisa J Gonzalez-Rothi
Unilateral C2 spinal cord hemisection (C2Hx) interrupts bulbospinal respiratory pathways innervating ipsilateral phrenic motoneurons, resulting in cessation of ipsilateral diaphragm motor output. Plasticity within the spinal neural circuitry controlling the diaphragm can induce partial recovery of phrenic bursting which correlates with the time-dependent return of spinal serotonin (5-HT) immunoreactivity in the vicinity of phrenic motoneurons. The 5-HT2A receptor subtype is present on phrenic motoneurons and its expression is up-regulated after cervical spinal cord injury; however the functional role of these receptors following injury has not been clearly defined...
July 12, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28711395/silymarin-ameliorates-experimentally-induced-depressive-like-behavior-in-rats-involvement-of-hippocampal-bdnf-signaling-inflammatory-cytokines-and-oxidative-stress-response
#9
Vishnu N Thakare, Manoj K Aswar, Yogesh P Kulkarni, Rajesh R Patil, Bhoomika M Patel
Silymarin is a polyphenolic flavonoid of Silybum marianum, exhibited neuroprotection and antidepressant like activity in acute restraint stressed mice. The main objective of the present study is to investigate possible antidepressant like activity of silymarin in experimentally induced depressive behavior in rats. The depressive behaviors were induced in rats by olfactory bulbectomized (OBX) technique. Wistar rats were administered with silymarin at a dose of 100mg/kg and 200mg/kg, by per oral in OBX and sham operated rats...
July 12, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28710888/chronic-spinal-cord-injury-causes-up-regulation-of-serotonin-5-ht-2a-and-2c-receptors-in-lumbosacral-cord-motoneurons
#10
Nailong Cao, Jianshu Ni, Xiaohu Wang, Hongjian Tu, Baojun Gu, Jiemin Si, Gang Wu, Karl-Erik Andersson
OBJECTIVES: To explore if the mechanism of the voiding dysfunction caused by spinal cord injury in rats can be improved by intravenous administration of the 5-HT2A/2C receptor agonist, DOI, and discuss whether it can be ascribed to serotonin 2A and 2C receptor up-regulation in lumbosacral cord motoneurons. MATERIALS AND METHODS: Female Sprague-Dawley rats were used, which were divided into two groups (Spinal cord injury group VS Normal control group). Under urethane anesthesia, cystometry was performed to examine the variation of urodynamic parameters before and after successive intrathecal administration of various doses of DOI into the lumbosacral cord...
July 15, 2017: BJU International
https://www.readbyqxmd.com/read/28706142/stress-inhibits-tryptophan-hydroxylase-expression-in-a-rat-model-of-depression
#11
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
https://www.readbyqxmd.com/read/28704274/maternal-separation-induces-long-term-effects-on-monoamines-and-brain-derived-neurotrophic-factor-levels-on-the-frontal-cortex-amygdala-and-hippocampus-differential-effects-after-a-stress-challenge
#12
Soledad Récamier-Carballo, Erika Estrada-Camarena, Carolina López-Rubalcava
The maternal separation (MS) paradigm is a well-known animal model that resembles the stress of early adverse life experiences and produces structural and functional abnormalities when animals are adults. The present study analyzed the effect of MS, in adult mice, on brain-derived neurotrophic factor (BDNF), serotonin (5-HT), and dopamine (DA) levels, and the turnover rate in the hippocampus, frontal cortex, and amygdala, and brain regions that are associated with emotion. Also, the effects of MS in depression-like responses in adult mice were studied...
July 12, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28701958/a-single-dose-of-lsd-does-not-alter-gene-expression-of-the-serotonin-2a-receptor-gene-htr2a-or-early-growth-response-genes-egr1-3-in-healthy-subjects
#13
Patrick C Dolder, Edna Grünblatt, Felix Müller, Stefan J Borgwardt, Matthias E Liechti
Rationale: Renewed interest has been seen in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. The repeated use of LSD leads to tolerance that is believed to result from serotonin (5-HT) 5-HT2A receptor downregulation. In rats, daily LSD administration for 4 days decreased frontal cortex 5-HT2A receptor binding. Additionally, a single dose of LSD acutely increased expression of the early growth response genes EGR1 and EGR2 in rat and mouse brains through 5-HT2A receptor stimulation...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28698386/antagonistic-serotonergic-and-octopaminergic-neural-circuits-mediate-food-dependent-locomotory-behavior-in-caenorhabditis-elegans
#14
Matthew A Churgin, Richard J McCloskey, Emily Peters, Christopher Fang-Yen
Biogenic amines are conserved signaling molecules that link food cues to behavior and metabolism in a wide variety of organisms. In the nematode C. elegans, the biogenic amines serotonin (5-HT) and octopamine regulate a number of food-related behaviors. Using a novel method for long-term quantitative behavioral imaging, we show that 5-HT and octopamine jointly influence locomotor activity and quiescence in feeding and fasting hermaphrodites, and we define the neural circuits through which this modulation occurs...
July 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28695708/targeting-fatty-acid-amide-hydrolase-and-transient-receptor-potential-vanilloid-1-simultaneously-to-modulate-colonic-motility-and-visceral-sensation-in-the-mouse-a-pharmacological-intervention-with-n-arachidonoyl-serotonin-aa-5-ht
#15
M Bashashati, J Fichna, F Piscitelli, R Capasso, A A Izzo, A Sibaev, J-P Timmermans, N Cenac, N Vergnolle, V Di Marzo, M Storr
BACKGROUND: Endocannabinoid anandamide (AEA) inhibits intestinal motility and visceral pain, but it may also be proalgesic through transient receptor potential vanilloid-1 (TRPV1). AEA is degraded by fatty acid amide hydrolase (FAAH). This study explored whether dual inhibition of FAAH and TRPV1 reduces diarrhea and abdominal pain. METHODS: Immunostaining was performed on myenteric plexus of the mouse colon. The effects of the dual FAAH/TRPV1 inhibitor AA-5-HT on electrically induced contractility, excitatory junction potential (EJP) and fast (f) and slow (s) inhibitory junction potentials (IJP) in the mouse colon, colonic propulsion and visceromotor response (VMR) to rectal distension were studied...
July 11, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28689254/desensitization-of-the-human-5-ht4-receptor-in-isolated-atria-of-transgenic-mice
#16
Ulrich Gergs, Julia Fritsche, Stephanie Fabian, Josepha Christ, Joachim Neumann
In the human cardiovascular system, serotonin (5-HT) exerts positive inotropic and chronotropic effects mediated by 5-HT4 receptors. Moreover, 5-HT4 receptor stimulation can cause arrhythmias in the human heart. Response to 5-HT can fade due to desensitization of the receptor system and/or activation of phosphodiesterases. In this study, we investigated a potential desensitization of the human 5-HT4(a) receptor expressed in the mouse heart. Therefore, we have used atrial preparations of transgenic (TG) mice with cardiac myocyte-specific overexpression of the human 5-HT4(a) receptor and their non-transgenic littermates (WT)...
July 8, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28688228/mast-cells-in-neuropathic-pain-an-increasing-spectrum-of-their-involvement-in-pathophysiology
#17
Gunjanpreet Kaur, Nirmal Singh, Amteshwar Singh Jaggi
Mast cells are immunological cells that are diversely distributed in different parts of the body. Their role in various pathological conditions such as hypersensitivity, atherosclerosis, pulmonary hypertension, and male infertility has been reported by different scientists. Apart from these, a number of studies have shown their important role in pathogenesis of neuropathic pain of diverse aetiology. They have been found to release active mediators, primarily histamine and serotonin on degranulation in response to different stimuli including chemical, nerve damage, toxin or disease-related conditions...
July 8, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28687505/xiaochaihutang-attenuates-depressive-anxiety-like-behaviors-of-social-isolation-reared-mice-by-regulating-monoaminergic-system-neurogenesis-and-bdnf-expression
#18
Jie Ma, Fang Wang, Jingyu Yang, Yingxu Dong, Guangyue Su, Kuo Zhang, Xing Pan, Ping Ma, Tingshuo Zhou, Chunfu Wu
ETHNOPHARMACOLOGICAL RELEVANCE: Xiaochaihutang (XCHT), as a classical herbal formula for the treatment of "Shaoyang syndrome" has been demonstrated to exert an antidepressant effect in multiple animal models of depression as shown in our previous studies. However, the effects of XCHT on social isolation (SI)-reared mice have not been investigated. This study aims to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice, and its implicated mechanisms, including alterations in the monoaminergic system, neurogenesis and neurotrophin expression...
July 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28684237/monoaminergic-toxicity-induced-by-cathinone-phthalimide-an-in-vitro-study
#19
Susan M Lantz, Hector Rosas-Hernandez, Elvis Cuevas, Bonnie Robinson, Kenner C Rice, William E Fantegrossi, Syed Z Imam, Merle G Paule, Syed F Ali
Bath salts, or synthetic cathinones, have cocaine-like or amphetamine-like properties and induce psychoactive effects via their capacity to modulate serotonin (5-HT) and dopamine (DA). Structurally distinct synthetic cathinones are continuously being generated to skirt existing drug laws. One example of these modified compounds is cathinone phthalimide (CP), which has already appeared on the global market. The lack of toxicological studies on the effects of CP on monoaminergic systems led to the development of the present study in order to generate an acute toxicity profile for CP, and to clarify whether it primarily affects both dopamine and serotonin, like the synthetic cathinones mephedrone and methylone, or primarily affects dopamine, like 3, 4-methylenedioxypyrovalerone (MDPV)...
July 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28683093/regulation-of-gut-luminal-serotonin-by-commensal-microbiota-in-mice
#20
Tomokazu Hata, Yasunari Asano, Kazufumi Yoshihara, Tae Kimura-Todani, Noriyuki Miyata, Xue-Ting Zhang, Shu Takakura, Yuji Aiba, Yasuhiro Koga, Nobuyuki Sudo
Gut lumen serotonin (5-hydroxytryptamine: 5-HT) contributes to several gastrointestinal functions such as peristaltic reflexes. 5-HT is released from enterochromaffin (EC) cells in response to a number of stimuli, including signals from the gut microbiota. However, the specific mechanism by which the gut microbiota regulates 5-HT levels in the gut lumen has not yet been clarified. Our previous work with gnotobiotic mice showed that free catecholamines can be produced by the deconjugation of conjugated catecholamines; hence, we speculated that deconjugation by bacterial enzymes may be one of the mechanisms whereby gut microbes can produce free 5-HT in the gut lumen...
2017: PloS One
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