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https://www.readbyqxmd.com/read/28198154/daily-and-seasonal-expression-profile-of-serum-melatonin-and-its-biosynthesizing-enzyme-genes-tph1-aanat1-aanat2-and-hiomt-in-pineal-organ-and-retina-a-study-under-natural-environmental-conditions-in-a-tropical-carp-catla-catla
#1
Chongtham Rajiv, Haobijam Sanjita Devi, Gopinath Mondal, Sijagurumayum Dharmajyoti Devi, Zeeshan Ahmad Khan, Thangal Yumnamcha, Rupjyoti Bharali, Asamanja Chattoraj
The tropical carp Catla catla is gaining importance for the studies of the impact of environmental changes on aquatic animals due to its surface dwelling habitat. To date, no information is available on the transcriptional profile of melatonin biosynthesizing enzyme genes in any tropical carp under either natural or artificial photothermal conditions in pineal and retina. The present study is an attempt to demonstrate the temporal pattern of expression of melatonin biosynthesizing enzyme genes, tryptophan hydroxylase 1 (tph1), arylalkylamine N-acetyltransferase (aanat1 and aanat2), and hydroxyindole-O-methyltransferase (hiomt) collectively and simultaneously in pineal organ and retina in tropical fish, C...
December 2016: Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology
https://www.readbyqxmd.com/read/28145470/genetic-polymorphisms-and-their-association-with-brain-and-behavioural-measures-in-heterogeneous-stock-mice
#2
Magdalena Janecka, Sarah J Marzi, Michael J Parsons, Lin Liu, Jose L Paya-Cano, Rebecca G Smith, Cathy Fernandes, Leonard C Schalkwyk
Although the search for quantitative trait loci for behaviour remains a considerable challenge, the complicated genetic architecture of quantitative traits is beginning to be understood. The current project utilised heterogeneous stock (HS) male mice (n = 580) to investigate the genetic basis for brain weights, activity, anxiety and cognitive phenotypes. We identified 126 single nucleotide polymorphisms (SNPs) in genes involved in regulation of neurotransmitter systems, nerve growth/death and gene expression, and subsequently investigated their associations with changes in behaviour and/or brain weights in our sample...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28109119/serotonin-transporter-protects-the-placental-cells-against-apoptosis-in-caspase-3-independent-pathway
#3
Coedy Hadden, Tariq Fahmi, Anthonya Cooper, Alena V Savenka, Vladimir V Lupashin, Drucilla J Roberts, Luc Maroteaux, Sylvie Hauguel-de Mouzon, Fusun Kilic
Serotonin (5-HT) and its specific transporter, SERT play important roles in pregnancy. Using placentas dissected from 18d gestational SERT-knock out (KO), peripheral 5-HT (TPH1)-KO and wild-type (WT) mice, we explored the role of 5-HT and SERT in placental functions in detail. An abnormal thick band of fibrosis and necrosis under the giant cell layer in SERT-KO placentas appeared only moderately in TPH1-KO and minimally present in WT placentas. The majority of the changes were located at the junctional zone of the placentas in SERT...
January 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28068779/norepinephrine-transporter-gene-variants-and-remission-from-depression-with-venlafaxine-treatment-in-older-adults
#4
Victoria S Marshe, Malgorzata Maciukiewicz, Soham Rej, Arun K Tiwari, Etienne Sibille, Daniel M Blumberger, Jordan F Karp, Eric J Lenze, Charles F Reynolds, James L Kennedy, Benoit H Mulsant, Daniel J Müller
OBJECTIVE: The primary objective of this study was to investigate five putatively functional variants of the norepinephrine transporter (SLC6A2, NET) and serotonin transporter (SLC6A4, SERT) genes and remission in depressed older adults treated with venlafaxine. A secondary objective was to analyze 17 other variants in serotonergic system genes (HTR1A, HTR2A, HTR1B, HTR2C, TPH1, TPH2) potentially involved in the mechanism of action of venlafaxine. METHOD: The sample included 350 adults age 60 or older with DSM-IV-defined major depressive disorder and a score of at least 15 on the Montgomery-Åsberg Depression Rating Scale (MADRS)...
January 10, 2017: American Journal of Psychiatry
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/27973928/tyrosine-and-tryptophan-hydroxylases-as-therapeutic-targets-in-human-disease
#6
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
#7
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/27871326/tryptophan-hydroxylase-1-and-5-ht7-receptor-preferentially-expressed-in-triple-negative-breast-cancer-promote-cancer-progression-through-autocrine-serotonin-signaling
#8
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/27866207/post-stroke-fatigue-may-be-associated-with-the-promoter-region-of-a-monoamine-oxidase-a-gene-polymorphism
#9
Smi Choi-Kwon, Mihye Ko, Sang-Eun Jun, Juhan Kim, Kyung-Hee Cho, Hyun-Wook Nah, Hasup Song, Jong S Kim
BACKGROUND: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. METHODS: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A)...
November 19, 2016: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/27796714/up-regulation-of-cathepsin-s-expression-by-hsp90-and-5-ht7-receptor-dependent-serotonin-signaling-correlates-with-triple-negativity-of-human-breast-cancer
#10
Jaya Gautam, Young Kyung Bae, Jung-Ae Kim
PURPOSE: Cathepsin S (CTSS) is expressed in a variety of cancers and stimulates tumor progression. However, the regulatory mechanism and role of CTSS in breast cancer progression are poorly understood. The aim of this study was to examine the relationships between CTSS expression and breast cancer grade and stage, and the signaling molecules involved in CTSS expression. METHODS: Immunohistochemical staining was performed in tissue microarray sections of 1451 human invasive breast cancer samples to determine epithelial (E-CTSS) and stromal CTSS (S-CTSS) expression...
October 27, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27779473/all-genes-encoding-enzymes-participating-in-melatonin-biosynthesis-in-the-chicken-pineal-gland-are-transcribed-rhythmically
#11
I Adamska, K Marhelava, D Walkiewicz, U Kedzierska, M Markowska, P M Majewski
Our recent research on the pineal gland of young chickens confirmed that three genes encoding enzymes involved in pineal melatonin biosynthesis, tryptophan hydroxylase 1 (Tph1), arylalkylamine-N-acetyltransferase (Aanat) and acetylserotonin O-methyltransferase (Asmt), are transcribed rhythmically under light:dark (L:D) 12:12 conditions in vivo. Additionally, in the pineal gland of maturing chickens, the dopa decarboxylase (Ddc) gene is transcribed rhythmically at a specific stage of the developmental process...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/27721799/genetic-association-studies-of-suicidal-behavior-a-review-of-the-past-10%C3%A2-years-progress-limitations-and-future-directions
#12
Bojan Mirkovic, Claudine Laurent, Marc-Antoine Podlipski, Thierry Frebourg, David Cohen, Priscille Gerardin
Suicidal behaviors (SBs), which range from suicidal ideation to suicide attempts and completed suicide, represent a fatal dimension of mental ill-health. The involvement of genetic risk factors in SB is supported by family, twin, and adoption studies. The aim of this paper is to review recent genetic association studies in SBs including (i) case-control studies, (ii) family-based association studies, and (iii) genome-wide association studies (GWAS). Various studies on genetic associations have tended to suggest that a number of genes [e...
2016: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/27672527/is-there-a-link-between-depressive-disorders-and-tryptophan-hydroxylase-1-tph1-gene-polymorphism-study-from-a-distressed-area-kashmir-india
#13
Raheel Mushtaq, Shah Faisal Ahmad Tarfarosh, Mohammad Maqbool Dar, Arshad Hussain, Sheikh Shoib, Tabindah Shah, Sahil Shah, Mushbiq Manzoor
BACKGROUND: The progress that man has made in all domains of life, during all these years of reign over the earth, is utterly remarkable. However, it always came at a price. Each epoch of progress has seen human beings inflicted with trauma and cynical consequences. During the last two decades, Kashmiri (Indian) people have experienced continuous violence, a reign of terror, and political turmoil. Each of these disastrous events has contributed to the increase in psychiatric disorders in this part of the world, especially major depressive disorders...
2016: Curēus
https://www.readbyqxmd.com/read/27638901/peripheral-serotonin-1b-receptor-transcription-predicts-the-effect-of-acute-tryptophan-depletion-on-risky-decision-making
#14
Paul Faulkner, Federico Mancinelli, Patricia L Lockwood, Mar Matarin, Raymond J Dolan, Nick W Wood, Peter Dayan, Jonathan P Roiser
BACKGROUND: The effects of acute tryptophan depletion on human decision-making suggest that serotonin modulates the processing of rewards and punishments. However, few studies have assessed which of the many types of serotonin receptors are responsible. METHODS: Using a within-subject, double-blind, sham-controlled design in 26 subjects, we examined whether individual differences in serotonin system gene transcription, measured in peripheral blood, predicted the effect of acute tryptophan depletion on decision-making...
October 3, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27603698/serotonin-deficiency-rescues-lactation-on-day-1-in-mice-fed-a-high-fat-diet
#15
Samantha R Weaver, Justin C Bohrer, Allan S Prichard, Paola K Perez, Liana J Streckenbach, Jake M Olson, Mark E Cook, Laura L Hernandez
Obesity is an inflammatory state associated with delayed lactogenesis stage II and altered mammary gland morphology. Serotonin mediates inflammation and mammary gland involution. The objective of this study was to determine if a genetic deficiency of tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis, would result in an improved ability to lactate in dams fed a high fat diet. Twenty-six female mice were fed a high (HFD) or low fat (LFD) diet throughout pregnancy and lactation...
2016: PloS One
https://www.readbyqxmd.com/read/27573591/personality-traits-as-an-endophenotype-in-genetic-studies-on-suicidality-in-bipolar-disorder
#16
J Pawlak, M Dmitrzak-Węglarz, M Maciukiewicz, P Kapelski, P Czerski, A Leszczyńska-Rodziewicz, D Zaremba, J Hauser
: Introduction The influence of personality traits on suicidal behaviour risk has been well documented. Personality traits and suicidal behaviour are partially genetically determined and personality has been described as an endophenotype of suicidal behaviour. The aim of this study was to investigate a possible association between personality traits with suicidal behaviour and selected serotonergic gene polymorphisms. METHODS: In the study we included 156 patients meeting DSM-IV criteria for bipolar disorder (BP) and 93 healthy controls...
August 30, 2016: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/27497328/tph1-a218-allele-is-associated-with-suicidal-behavior-in-turkish-population
#17
Onur Beden, Ender Senol, Sevcan Atay, Handan Ak, Ayse Ender Altintoprak, Guclu Selahattin Kiyan, Buket Petin, Utku Yaman, Hikmet Hakan Aydin
BACKGROUND: Serotonergic dysfunction is implicated in depression, psychiatric disorders and suicidal behaviors. The first and rate-limiting step in the synthesis of serotonin is catalyzed by tryptophan hydroxylase (TPH) which is encoded by TPH1 and THP2 genes. Genetic association studies have revealed contradictory results about the effect of the TPH1 A218C (rs1800532) polymorphism on suicidal behavior in different populations. MATERIAL AND METHOD: In this study, we investigated A218C polymorphism in 109 suicide attempters and 98 healthy controls...
July 2016: Legal Medicine
https://www.readbyqxmd.com/read/27479537/suicide-behavior-as-a-quantitative-trait-and-its-genetic-background
#18
Joanna Pawlak, Monika Dmitrzak-Weglarz, Monika Wilkosc, Aleksandra Szczepankiewicz, Anna Leszczynska-Rodziewicz, Dorota Zaremba, Pawel Kapelski, Aleksandra Rajewska-Rager, Joanna Hauser
INTRODUCTION: Studies have not given yet a clear answer what is the genetic background of suicidal predisposition. The associations between polymorphisms of the TPH1 and 5-HTTLPR genes and violent suicidal behavior was revealed with the least inconsistencies. METHOD: We selected 10 "strong candidate genes" and 35 SNPs, SLC6A4 and ACP1 for replication study. We searched associations between precisely described suicidal phenotype in 825 affective patients and polymorphisms of selected neurobiological pathways genes as well as their interactions that constitute suicidal risk...
July 19, 2016: Journal of Affective Disorders
https://www.readbyqxmd.com/read/27444653/serotonin-biosynthesis-as-a-predictive-marker-of-serotonin-pharmacodynamics-and-disease-induced-dysregulation
#19
Richard W D Welford, Magali Vercauteren, Annette Trébaul, Christophe Cattaneo, Doriane Eckert, Marco Garzotti, Patrick Sieber, Jérôme Segrestaa, Rolf Studer, Peter M A Groenen, Oliver Nayler
The biogenic amine serotonin (5-HT) is a multi-faceted hormone that is synthesized from dietary tryptophan with the rate limiting step being catalyzed by the enzyme tryptophan hydroxylase (TPH). The therapeutic potential of peripheral 5-HT synthesis inhibitors has been demonstrated in a number of clinical and pre-clinical studies in diseases including carcinoid syndrome, lung fibrosis, ulcerative colitis and obesity. Due to the long half-life of 5-HT in blood and lung, changes in steady-state levels are slow to manifest themselves...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27293961/association-study-between-promoter-polymorphism-of-tph1-and-progression-of-idiopathic-scoliosis
#20
Vasil Yablanski, Svetla Nikolova, Evgeni Vlaev, Alexey Savov, Ivo Kremensky
The concept of disease-modifier genes as an element of genetic heterogeneity has been widely accepted and reported. The aim of the current study is to investigate the association between the promoter polymorphism TPH1 (rs10488682) and progression of idiopathic scoliosis (IS) in Eastern European population sample. A total of 105 patients and 210 healthy gender-matched controls were enrolled in this study. The TPH1 promoter polymorphism was genotyped by amplification followed by restriction. The statistical analysis was performed by Fisher's Exact Test...
2016: Journal of Biomarkers
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