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tryptophan hydroxylase

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https://www.readbyqxmd.com/read/28087339/differential-behavioral-sensitivity-to-carbon-dioxide-co2-inhalation-in-rats
#1
Andrew Winter, Rebecca Ahlbrand, Devanshi Naik, Renu Sah
Inhalation of carbon dioxide (CO2) is frequently employed as a biological challenge to evoke intense fear and anxiety. In individuals with panic disorder, CO2 reliably evokes panic attacks. Sensitivity to CO2 is highly heterogeneous among individuals, and although a genetic component is implicated, underlying mechanisms are not clear. Preclinical models that can simulate differential responsivity to CO2 are therefore relevant. In the current study we investigated CO2-evoked behavioral responses in four different rat strains: Sprague-Dawley (SD), Wistar (W), Long Evans (LE) and Wistar-Kyoto, (WK) rats...
January 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28086815/antibiotics-induced-depletion-of-mice-microbiota-induces-changes-in-host-serotonin-biosynthesis-and-intestinal-motility
#2
Xiaolong Ge, Chao Ding, Wei Zhao, Lizhi Xu, Hongliang Tian, Jianfeng Gong, Minsheng Zhu, Jieshou Li, Ning Li
BACKGROUND: The gastrointestinal motility is affected by gut microbiota and the relationship between them has become a hot topic. However, mechanisms of microbiota in regulating motility have not been well defined. We thus investigated the effect of microbiota depletion by antibiotics on gastrointestinal motility, colonic serotonin levels, and bile acids metabolism. METHODS: After 4 weeks with antibiotics treatments, gastrointestinal and colon transit, defecation frequency, water content, and other fecal parameters were measured and analyzed in both wild-type and antibiotics-treated mice, respectively...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28069454/c1473g-polymorphism-in-mouse-tryptophan-hydroxylase-2-gene-in-the-regulation-of-the-reaction-to-emotional-stress
#3
Ekaterina Y Bazhenova, Daria V Bazovkina, Elizabeth A Kulikova, Dariya V Fursenko, Nikita V Khotskin, Daria V Lichman, Alexander V Kulikov
Neurotransmitter serotonin (5-HT) is involved in the regulation of stress response. Tryptophan hydroxylase-2 (TPH2) is the key enzyme of serotonin (5-HT) synthesis in the brain. C1473G polymorphism in Tph2 gene is the main factor defining the enzyme activity in the brain of laboratory mice. The effect of interaction between C1473G polymorphism and 30min restriction stress on the behavior in the open field test, c-Fos gene expression and 5-HT metabolism in the brain in adult male of B6-1473C and B6-1473G congenic mouse lines with high and low TPH2 activity was investigated...
January 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28054193/personality-as-an-intermediate-phenotype-for-genetic-dissection-of-alcohol-use-disorder
#4
REVIEW
Lars Oreland, Gianvito Lagravinese, Simone Toffoletto, Kent W Nilsson, Jaanus Harro, C Robert Cloninger, Erika Comasco
Genetic and environmental interactive influences on predisposition to develop alcohol use disorder (AUD) account for the high heterogeneity among AUD patients and make research on the risk and resiliency factors complicated. Several attempts have been made to identify the genetic basis of AUD; however, only few genetic polymorphisms have consistently been associated with AUD. Intermediate phenotypes are expected to be in-between proxies of basic neuronal biological processes and nosological symptoms of AUD...
January 4, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28041831/optimization-of-spirocyclic-proline-tryptophan-hydroxylase-1-inhibitors
#5
Daniel R Goldberg, Stéphane De Lombaert, Robert Aiello, Patricia Bourassa, Nicole Barucci, Qing Zhang, Vishwas Paralkar, Adam J Stein, Melissa Holt, Jim Valentine, William Zavadoski
As a follow-up to the discovery of our spirocyclic proline-based TPH1 inhibitor lead, we describe the optimization of this scaffold. Through a combination of X-ray co-crystal structure guided design and an in vivo screen, new substitutions in the lipophilic region of the inhibitors were identified. This effort led to new TPH1 inhibitors with in vivo efficacy when dosed as their corresponding ethyl ester prodrugs. In particular, 15b (KAR5585), the prodrug of the potent TPH1 inhibitor 15a (KAR5417), showed robust reduction of intestinal serotonin (5-HT) levels in mice...
December 23, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28031476/5-hydroxytryptamine-synthesized-in-the-aorta-gonad-mesonephros-regulates-hematopoietic-stem-and-progenitor-cell-survival
#6
Junhua Lv, Lu Wang, Ya Gao, Yu-Qiang Ding, Feng Liu
The in vitro or ex vivo production of transplantable hematopoietic stem cells (HSCs) holds great promise for the treatment of hematological diseases in the clinic. However, HSCs have not been produced from either embryonic or induced pluripotent stem cells. In this study, we report that 5-hydroxytryptamine (5-HT; also called serotonin) can enhance the generation of hematopoietic stem and progenitor cells (HSPCs) in vitro and is essential for the survival of HSPCs in vivo during embryogenesis. In tryptophan hydroxylase 2-deficient embryos, a decrease in 5-HT synthesized in the aorta-gonad-mesonephros leads to apoptosis of nascent HSPCs...
December 28, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28029782/a-tph2-gfp-reporter-stem-cell-line-to-model-in-vitro-and-in-vivo-serotonergic-neuron-development-and-function
#7
Giulia Pacini, Attilio Marino, Sara Migliarini, Elisa Brilli, Barbara Pelosi, Giacomo Maddaloni, Marta Pratelli, Mario Pellegrino, Aldo Ferrari, Massimo Pasqualetti
Modeling biological systems in vitro has contributed to clarification of complex mechanisms in simplified and controlled experimental conditions. Mouse embryonic stem (mES) cells can be successfully differentiated toward specific neuronal cell fates, thus representing an attractive tool to dissect, in vitro, mechanisms that underlie complex neuronal features. In this study, we generated and characterized a reporter mES cell line, called Tph2(GFP), in which the vital reporter GFP replaces the tryptophan hydroxylase 2 (Tph2) gene...
January 19, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28013484/antidepressant-like-effects-of-ginsenoside-rg3-in-mice-via-activation-of-the-hippocampal-bdnf-signaling-cascade
#8
Zhengchen You, Qi Yao, Jianhong Shen, Zhikai Gu, Hui Xu, Zhonghua Wu, Chuanjun Chen, Luozhu Li
Current antidepressants are clinically effective only after several weeks of administration. Ginsenoside Rg3 is one component of ginsenosides, with a similar chemical structure to ginsenoside Rg1. Here, we investigated the antidepressant effects of Rg3 in mouse models of depression. The antidepressant actions of Rg3 were first examined in the forced swim test (FST) and tail suspension test (TST), and then assessed in the chronic social defeat stress (CSDS) model of depression. The changes in the hippocampal brain-derived neurotrophic factor (BDNF) signaling pathway after CSDS and Rg3 treatment were investigated...
December 24, 2016: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28008302/benefits-of-hormone-therapy-estrogens-depend-on-estrogen-type-17%C3%AE-estradiol-and-conjugated-equine-estrogens-have-differential-effects-on-cognitive-anxiety-like-and-depressive-like-behaviors-and-increase-tryptophan-hydroxylase-2-mrna-levels-in-dorsal-raphe-nucleus
#9
Ryoko Hiroi, Giulia Weyrich, Stephanie V Koebele, Sarah E Mennenga, Joshua S Talboom, Lauren T Hewitt, Courtney N Lavery, Perla Mendoza, Ambra Jordan, Heather A Bimonte-Nelson
Decreased serotonin (5-HT) function is associated with numerous cognitive and affective disorders. Women are more vulnerable to these disorders and have a lower rate of 5-HT synthesis than men. Serotonergic neurons in the dorsal raphe nucleus (DRN) are a major source of 5-HT in the forebrain and play a critical role in regulation of stress-related disorders. In particular, polymorphisms of tryptophan hydroxylase-2 (TpH2, the brain-specific, rate-limiting enzyme for 5-HT biosynthesis) are implicated in cognitive and affective disorders...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27994633/electroacupuncture-restores-5-ht-system-deficit-in-chronic-mild-stress-induced-depressed-rats
#10
Dongmei Duan, Ya Tu, Xiuyan Yang, Ping Liu
Objective. The current study is designed to investigate the antidepressant efficacy of electroacupuncture (EA) treatment by evaluating its effect on the synthesis, metabolism, reuptake, and receptors of 5-hydroxytryptamine (5-HT), so as to clarify the molecular mechanisms of EA for antidepression. Materials and Methods. Solitary combined with the chronic unpredictable mild stress (CUMS) was used to establish the rat model with depression. The depressed rats were supplied with EA treatment for 4 weeks, and the behavior change and the following indices including 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), monoamine oxidase A (MAO-A), tryptophan hydroxylase (TPH), 5-HT transporter (SERT), 5-HT1A, and 5-HT2A in hippocampus and prefrontal cortex were examined...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27989490/paraphilic-sexual-offenders-do-not-differ-from-control-subjects-with-respect-to-dopamine-and-serotonin-related-genetic-polymorphisms
#11
Andrzej Jakubczyk, Aleksandra Krasowska, Marcin Bugaj, Maciej Kopera, Anna Klimkiewicz, Agata Łoczewska, Aneta Michalska, Aleksandra Majewska, Natalia Szejko, Anna Podgórska, Małgorzata Sołowiej, Leszek Markuszewski, Sławomir Jakima, Rafał Płoski, Kirk Brower, Marcin Wojnar
INTRODUCTION: Rape and pedophilic child molestation are the most commonly convicted sexual offenses in Poland. Recent studies have suggested a possible genetic contribution toward pathologic sexual interests and behaviors. AIM: To analyze and compare functional polymorphisms of genes associated with the activity of the serotonin and dopamine systems in a group of paraphilic sexual offenders and control subjects. METHODS: The study sample (n = 97) consisted of two groups: paraphilic sexual offenders (65 pedophilic child molesters and 32 rapists) and controls (n = 76)...
December 15, 2016: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/27983993/lentiviral-vector-driven-inhibition-of-5-ht-synthesis-in-b3-bulbo-spinal-serotonergic-projections-consequences-on-nociception-inflammatory-and-neuropathic-pain-in-rats
#12
Anne Gautier, Hanady El Ouaraki, Natacha Bazin, Soha Salam, Guilan Vodjdani, Sylvie Bourgoin, Sophie Pezet, Jean-François Bernard, Michel Hamon
Although it is well established that bulbo-spinal serotonergic projections contribute to pain control mechanisms, whether they exert anti- or pro-nociceptive modulations is still a matter of debate. In order to reappraise the role of 5-HT in descending controls, we used RNA interference to selectively inhibit 5-HT synthesis in B3 neurons and assess resulting changes in nociception. Rats were injected into the bulbar B3 group with a recombinant lentiviral vector, LV-shTPH2, encoding RNA interfering with tryptophan hydroxylase 2 expression...
February 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27981176/effects-of-aging-on-stress-related-responses-of-serotonergic-neurons-in-the-dorsal-raphe-nucleus-of-male-rats
#13
Naoko Yamaguchi, Noriaki Nakajima, Shoshiro Okada, Kazunari Yuri
Responses to various stressors in the brain change with age. However, little is known about the neural mechanisms underlying age-dependent changes in stress responses. It is known that serotonin, a stress-related transmitter, is closely related with the regulation of stress responses in the brain and that serotonergic function is modulated by various factors, including estrogen, in both sexes. In the present study, to elucidate the effects of aging on stress responses in serotonergic neurons, we examined the expression levels of tryptophan hydroxylase (TPH; a marker of serotonergic neurons) in the dorsal, ventral and lateral parts of the dorsal raphe nucleus (DRN) in young and old intact male rats...
June 2016: Neurobiology of Stress
https://www.readbyqxmd.com/read/27973928/tyrosine-and-tryptophan-hydroxylases-as-therapeutic-targets-in-human-disease
#14
Kai Waløen, Rune Kleppe, Aurora Martinez, Jan Haavik
The ancient and ubiquitous monoamine signalling molecules serotonin, dopamine, norepinephrine, and epinephrine are involved in multiple physiological functions. The aromatic amino acid hydroxylases tyrosine hydroxylase (TH), tryptophan hydroxylase 1 (TPH1), and tryptophan hydroxylase 2 (TPH2) catalyse the rate-limiting steps in the biosynthesis of these monoamines. Genetic variants of TH, TPH1, and TPH2 genes are associated with neuropsychiatric disorders. The interest in these enzymes as therapeutic targets is increasing as new roles of these monoamines have been discovered, not only in brain function and disease, but also in development, cardiovascular function, energy and bone homeostasis, gastrointestinal motility, hemostasis, and liver function...
December 26, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27927914/tryptophan-hydroxylase-1-inhibition-impacts-pulmonary-vascular-remodeling-in-two-rat-models-of-pulmonary-hypertension
#15
Robert J Aiello, Patricia-Ann Bourassa, Qing Zhang, Jeffrey Dubins, Daniel R Goldberg, Stéphane De Lombaert, Marc Humbert, Christophe Guignabert, Maria A Cavasin, Timothy A McKinsey, Vishwas Paralkar
Pulmonary arterial hypertension (PAH) is a progressive disease defined by a chronic elevation in pulmonary arterial pressure with extensive pulmonary vascular remodeling and perivascular inflammation characterized by an accumulation of macrophages, lymphocytes, dendritic cells, and mast cells. Although the exact etiology of the disease is unknown, clinical as well as preclinical data strongly implicate a role for serotonin (5-HT) in the process. Here, we investigated the chronic effects of pharmacological inhibition of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in peripheral 5-HT biosynthesis, in two preclinical models of pulmonary hypertension (PH), the monocrotaline (MCT) rat and the semaxanib (SUGEN, Medinoah, Suzhou, China)-hypoxia rat...
February 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27918724/telotristat-ethyl-a-tryptophan-hydroxylase-inhibitor-for-the-treatment-of-carcinoid-syndrome
#16
Matthew H Kulke, Dieter Hörsch, Martyn E Caplin, Lowell B Anthony, Emily Bergsland, Kjell Öberg, Staffan Welin, Richard R P Warner, Catherine Lombard-Bohas, Pamela L Kunz, Enrique Grande, Juan W Valle, Douglas Fleming, Pablo Lapuerta, Phillip Banks, Shanna Jackson, Brian Zambrowicz, Arthur T Sands, Marianne Pavel
Purpose Preliminary studies suggested that telotristat ethyl, a tryptophan hydroxylase inhibitor, reduces bowel movement (BM) frequency in patients with carcinoid syndrome. This placebo-controlled phase III study evaluated telotristat ethyl in this setting. Patients and Methods Patients (N = 135) experiencing four or more BMs per day despite stable-dose somatostatin analog therapy received (1:1:1) placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg three times per day orally during a 12-week double-blind treatment period...
January 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27896310/preservation-of-essential-odor-guided-behaviors-and-odor-based-reversal-learning-after-targeting-adult-brain-serotonin-synthesis
#17
Kaitlin S Carlson, Meredith S Whitney, Marie A Gadziola, Evan S Deneris, Daniel W Wesson
The neurotransmitter serotonin (5-HT) is considered a powerful modulator of sensory system organization and function in a wide range of animals. The olfactory system is innervated by midbrain 5-HT neurons into both its primary and secondary odor-processing stages. Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function, including odor information input to the olfactory bulb. It is unknown, however, whether the olfactory system requires 5-HT for even its most basic behavioral functions...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27871326/tryptophan-hydroxylase-1-and-5-ht7-receptor-preferentially-expressed-in-triple-negative-breast-cancer-promote-cancer-progression-through-autocrine-serotonin-signaling
#18
Jaya Gautam, Suhrid Banskota, Sushil Chandra Regmi, Subi Ahn, Yong Hyun Jeon, Hyunyoung Jeong, Seung Joo Kim, Tae-Gyu Nam, Byeong-Seon Jeong, Jung-Ae Kim
BACKGROUND: Triple-negative breast cancer (TNBC) has a high risk of relapse and there are few chemotherapy options. Although 5-hydroxytryptamine (5-HT, serotonin) signaling pathways have been suggested as potential targets for anti-cancer drug development, the mechanism responsible for the action of 5-HT in TNBC remains unknown. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to measure mRNA and protein levels, respectively...
November 21, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27871272/association-of-tryptophan-hydroxylase-2-polymorphisms-with-oppositional-defiant-disorder-in-a-chinese-han-population
#19
Chang-Hong Wang, Cong Liu, En-Zhao Cong, Gai-Ling Xu, Ting-Ting Lv, Ying-Li Zhang, Qiu-Fen Ning, Ji-Kang Wang, Hui-Yao Nie, Yan Li
BACKGROUND: Oppositional defiant disorder (ODD) is a behavioral disorder of school-age population. It is well known that 5-HT dysfunction is correlated with impulsivity, which is one of the common characteristics of ODD. The enzyme tryptophan hydroxylase-2 (TPH-2) synthesizes 5-HT in serotonergic neurons of the midbrain raphe. The purposes of this study were to investigate the potential association of TPH-2 polymorphisms with susceptibility to ODD in a Han Chinese school population. METHODS: Four polymorphisms (rs4570625, rs11178997, rs1386494 and rs7305115) of the TPH-2 gene were analyzed by using polymerase chain reaction and DNA microarray hybridization in a case-control study of 276 Han Chinese individuals (124 ODD and 152 controls)...
November 21, 2016: Behavioral and Brain Functions: BBF
https://www.readbyqxmd.com/read/27869229/tetratricopeptide-repeat-domain-9a-modulates-anxiety-like-behavior-in-female-mice
#20
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
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