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https://www.readbyqxmd.com/read/28443016/genetics-of-aggression-in-alzheimer-s-disease-ad
#1
Walter J Lukiw, Evgeny I Rogaev
Alzheimer's disease (AD) is a terminal, age-related neurological syndrome exhibiting progressive cognitive and memory decline, however AD patients in addition exhibit ancillary neuropsychiatric symptoms (NPSs) and these include aggression. In this communication we provide recent evidence for the mis-regulation of a small family of genes expressed in the human hippocampus that appear to be significantly involved in expression patterns common to both AD and aggression. DNA array- and mRNA transcriptome-based gene expression analysis and candidate gene association and/or genome-wide association studies (CGAS, GWAS) of aggressive attributes in humans have revealed a surprisingly small subset of six brain genes that are also strongly associated with altered gene expression patterns in AD...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28404880/serotonergic-system-antagonists-target-breast-tumor-initiating-cells-and-synergize-with-chemotherapy-to-shrink-human-breast-tumor-xenografts
#2
William D Gwynne, Robin M Hallett, Adele Girgis-Gabardo, Bojana Bojovic, Anna Dvorkin-Gheva, Craig Aarts, Kay Dias, Anita Bane, John A Hassell
Breast tumors comprise an infrequent tumor cell population, termed breast tumor initiating cells (BTIC), which sustain tumor growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC to provide more durable breast cancer remissions than are currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse BTIC resident in the mammary tumors of a HER2-overexpressing model of breast cancer. Here we report that antagonists of serotonin (5-hydroxytryptamine; 5-HT) biosynthesis and activity, including US Federal Food and Drug Administration (FDA)-approved antidepressants, targeted BTIC resident in numerous breast tumor cell lines regardless of their clinical or molecular subtype...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28321510/dna-methylation-patterns-of-behavior-related-gene-promoter-regions-dissect-the-gray-wolf-from-domestic-dog-breeds
#3
Zsofia Banlaki, Giulia Cimarelli, Zsofia Viranyi, Eniko Kubinyi, Maria Sasvari-Szekely, Zsolt Ronai
A growing body of evidence highlights the relationship between epigenetics, especially DNA methylation, and population divergence as well as speciation. However, little is known about how general the phenomenon of epigenetics-wise separation of different populations is, or whether population assignment is, possible based on solely epigenetic marks. In the present study, we compared DNA methylation profiles between four different canine populations: three domestic dog breeds and their ancestor the gray wolf...
March 21, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28315323/increased-serotonin-signaling-contributes-to-the-warburg-effect-in-pancreatic-tumor-cells-under-metabolic-stress-and-promotes-growth-of-pancreatic-tumors-in-mice
#4
Shu-Heng Jiang, Jun Li, Fang-Yuan Dong, Jian-Yu Yang, De-Jun Liu, Xiao-Mei Yang, Ya-Hui Wang, Min-Wei Yang, Xue-Liang Fu, Xiao-Xin Zhang, Qing Li, Xiu-Feng Pang, Yan-Miao Huo, Jiao Li, Jun-Feng Zhang, Ho-Young Lee, Su-Jae Lee, Wen-Xin Qin, Jian-Ren Gu, Yong-Wei Sun, Zhi-Gang Zhang
BACKGROUND & AIMS: The desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors. METHODS: We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras(G12D/+); Trp53(R172H/+); Pdx1-Cre; (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples...
March 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28295297/comparative-analysis-of-monoaminergic-cerebrospinal-fluid-contacting-cells-in-osteichthyes-bony-vertebrates
#5
Anna L Xavier, Romain Fontaine, Solal Bloch, Pierre Affaticati, Arnim Jenett, Michaël Demarque, Philippe Vernier, Kei Yamamoto
Cerebrospinal fluid-contacting (CSF-c) cells containing monoamines such as dopamine (DA) and serotonin (5-HT) occur in the periventricular zones of the hypothalamic region of most vertebrates except for placental mammals. Here we compare the organization of the CSF-c cells in chicken, Xenopus, and zebrafish, by analyzing the expression of synthetic enzymes of DA and 5-HT, respectively, tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), and draw an evolutionary scenario for this cell population. Due to the lack of TH immunoreactivity in this region, the hypothalamic CSF-c cells have been thought to take up DA from the ventricle instead of synthesizing it...
March 14, 2017: Journal of Comparative Neurology
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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)...
2017: 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
#15
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
#16
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
#17
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
#18
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...
July 6, 2016: Curēus
https://www.readbyqxmd.com/read/27638901/peripheral-serotonin-1b-receptor-transcription-predicts-the-effect-of-acute-tryptophan-depletion-on-risky-decision-making
#19
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
#20
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
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