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https://www.readbyqxmd.com/read/29145497/rare-genetic-variants-in-the-endocannabinoid-system-genes-cnr1-and-dagla-are-associated-with-neurological-phenotypes-in-humans
#1
Douglas R Smith, Christine M Stanley, Theodore Foss, Richard G Boles, Kevin McKernan
Rare genetic variants in the core endocannabinoid system genes CNR1, CNR2, DAGLA, MGLL and FAAH were identified in molecular testing data from 6,032 patients with a broad spectrum of neurological disorders. The variants were evaluated for association with phenotypes similar to those observed in the orthologous gene knockouts in mice. Heterozygous rare coding variants in CNR1, which encodes the type 1 cannabinoid receptor (CB1), were found to be significantly associated with pain sensitivity (especially migraine), sleep and memory disorders-alone or in combination with anxiety-compared to a set of controls without such CNR1 variants...
2017: PloS One
https://www.readbyqxmd.com/read/29120578/role-of-cannabinoid-cb2-receptor-gene-cnr2-polymorphism-in-children-with-immune-thrombocytopenic-purpura-in-beni-suef-governorate-in-egypt
#2
Dina A Ezzat, Amira A Hammam, Waleed M El-Malah, Rasha A Khattab, Eman M Mangoud
The cannabinoid system is involved in the immune regulation by modulation of Th cells type 1 and 2. It is composed of the CB2 receptor which is expressed at 10 to 100 folds greater levels on immune cells than the CB1 receptors. The CB2 is encoded by the cannabinoid CB receptor gene (CNR2) gene. This study aims to investigate the polymorphism in CNR2 gene variation rs 35761398 (Q63R) in Egyptian children with immune thrombocytopenic purpura and to investigate the relation between this gene polymorphism and either the susceptibility to or the chronicity of the disease...
January 2017: Egyptian Journal of Immunology
https://www.readbyqxmd.com/read/29105060/cannabinoid-receptor-1-2-double-knockout-mice-develop-epilepsy
#3
Shane Rowley, Xiaofei Sun, Isabel V Lima, Alexandra Tavenier, Antonio Carlos Pinheiro de Oliveira, Sudhansu K Dey, Steve C Danzer
The endocannabinoid system has gained attention as an important modulator of activity in the central nervous system. Initial studies focused on cannabinoid receptor 1 (CB1), which is widely expressed in the brain, but recent work also implicates cannabinoid receptor 2 (CB2) in modulating neuronal activity. Both receptors are capable of reducing neuronal activity, generating interest in cannabinoid receptor agonists as potential anticonvulsants. CB1 (Cnr1) and CB2 (Cnr2) single-knockout mice have been generated, with the former showing heightened seizure sensitivity, but not overt seizures...
November 3, 2017: Epilepsia
https://www.readbyqxmd.com/read/28992427/effects-of-cannabinoid-receptor-type-2-in-respiratory-syncytial-virus-infection-in-human-subjects-and-mice
#4
Alireza Tahamtan, Yazdan Samieipoor, Fatemeh Sadat Nayeri, Ali Akbar Rahbarimanesh, Anahita Izadi, Ali Rashidi-Nezhad, Masoumeh Tavakoli-Yaraki, Mohammad Farahmand, Louis Bont, Fazel Shokri, Talat Mokhatri-Azad, Vahid Salimi
An accumulating body of evidence suggests that the endocannabinoid system plays a significant role in pathophysiological processes and impacts disease severity. Here we investigate the possible role of a cannabinoid receptor type 2 (CB2) functional variant in determining disease severity and the potential pharmacological therapeutic effects of CB2 activation in viral respiratory infection. The common missense variant (CAA/CGG; Q63R) of the gene-encoding CB2 receptor (CNR2) was evaluated in 90 inpatient and 90 outpatient children with acute respiratory tract infection (ARTI)...
October 9, 2017: Virulence
https://www.readbyqxmd.com/read/28895540/polymorphism-rs3123554-in-the-cannabinoid-receptor-gene-type-2-cnr2-reveals-effects-on-body-weight-and-insulin-resistance-in-obese-subjects
#5
Daniel Antonio de Luis, Olatz Izaola, David Primo, Beatriz de la Fuente, Rocio Aller
BACKGROUND: Few studies assessing the relationship between single nucleotide polymorphisms in CNR2 and obesity or its related metabolic parameters are available. OBJECTIVE: To investigate the influence of polymorphism rs3123554 in the CNR2 receptor gene on obesity anthropometric parameters, insulin resistance, and adipokines in subjects with obesity. DESIGN: The study population consisted of 1027 obese subjects, who were performed bioelectrical impedance analyses, blood pressure measurements, serial assessments of dietary intake during three days, and biochemical tests...
October 2017: Endocrinología, diabetes y nutrición
https://www.readbyqxmd.com/read/28837063/daytime-dependent-changes-of-cannabinoid-receptor-type-1-and-type-2-expression-in-rat-liver
#6
Ivonne Bazwinsky-Wutschke, Alexander Zipprich, Faramarz Dehghani
The present study was performed to investigate the diurnal expression pattern of cannabinoid receptor type 1 (CB₁) and type 2 (CB₂) in liver tissue of 12- and 51-week-old normoglycemic Wistar rats. By using real-time RT-PCR, daytime dependent changes in both age groups and, for both, hepatic Cnr1 and Cnr2 receptor mRNA levels were measured. Highest amount of mRNA was detected in the light period (ZT3, ZT6, and ZT9) while the lowest amount was measured in the dark period (ZT18 and ZT21). Diurnal transcript expression pattern was accompanied by comparable changes of protein level for CB₁, as shown by Western blotting...
August 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28826718/contrasting-effects-of-selective-magl-and-faah-inhibition-on-dopamine-depletion-and-gdnf-expression-in-a-chronic-mptp-mouse-model-of-parkinson-s-disease
#7
Noemi Pasquarelli, Christoph Porazik, Hanna Bayer, Eva Buck, Stefan Schildknecht, Patrick Weydt, Anke Witting, Boris Ferger
The modulation of the brain endocannabinoid system has been identified as an option to treat neurodegenerative diseases including Parkinson's disease (PD). Especially the elevation of endocannabinoid levels by inhibition of hydrolytic degradation represents a valuable approach. To evaluate whether monoacylglycerol lipase (MAGL) or fatty acid amide hydrolase (FAAH) inhibition could be beneficial for PD, we examined in parallel the therapeutic potential of the highly selective MAGL inhibitor KML29 elevating 2-arachidonoylglyerol (2-AG) levels and the highly selective FAAH inhibitor PF-3845 elevating anandamide (AEA) levels in a chronic methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/probenecid) mouse model of PD...
August 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28759568/cannabinoid-receptor-2-63-rr-variant-is-independently-associated-with-severe-necroinflammation-in-hiv-hcv-coinfected-patients
#8
Caterina Sagnelli, Caterina Uberti-Foppa, Hamid Hasson, Giulia Bellini, Carmine Minichini, Stefania Salpietro, Emanuela Messina, Diletta Barbanotti, Marco Merli, Francesca Punzo, Nicola Coppola, Adriano Lazzarin, Evangelista Sagnelli, Francesca Rossi
OBJECTIVE: This is the first study to analyze the impact of the rs35761398 variant of the CNR2 gene leading to the substitution of GLN (Q) of codon 63 of the cannabinoid receptor 2 (CB2) with ARG (R) on the clinical presentation of chronic hepatitis in HIV/HCV coinfected patients. METHODS: Enrolled in this study were 166 consecutive HIV/HCV coinfected patients, naïve for HCV treatment. A pathologist unaware of the patients' condition graded liver fibrosis, necroinflammation (Ishak) and steatosis...
2017: PloS One
https://www.readbyqxmd.com/read/28752643/combined-deficiency-of-the-cnr1-and-cnr2-receptors-protects-against-age-related-bone-loss-by-osteoclast-inhibition
#9
Antonia Sophocleous, Silvia Marino, Dilruba Kabir, Stuart H Ralston, Aymen I Idris
The endocannabinoid system plays a role in regulating bone mass and bone cell activity and inactivation of the type 1 (Cnr1) or type 2 (Cnr2) cannabinoid receptors influences peak bone mass and age-related bone loss. As the Cnr1 and Cnr2 receptors have limited homology and are activated by different ligands, we have evaluated the effects of combined deficiency of Cnr1 and 2 receptors (Cnr1/2(-/-) ) on bone development from birth to old age and studied ovariectomy induced bone loss in female mice. The Cnr1/2(-/-) mice had accelerated bone accrual at birth when compared with wild type littermates, and by 3 months of age, they had higher trabecular bone mass...
October 2017: Aging Cell
https://www.readbyqxmd.com/read/28716266/sativex%C3%A2-effects-on-promoter-methylation-and-on-cnr1-cnr2-expression-in-peripheral-blood-mononuclear-cells-of-progressive-multiple-sclerosis-patients
#10
Massimo Santoro, Massimiliano Mirabella, Chiara De Fino, Assunta Bianco, Matteo Lucchini, Francesco Losavio, Andrea Sabino, Viviana Nociti
Multiple sclerosis (MS) is a chronic demyelinating central nervous system (CNS) disease that involve oligodendrocyte loss and failure to remyelinate damaged brain areas causing a progressive neurological disability. Studies in MS mouse model suggest that cannabinoids ameliorate symptoms as spasticity, tremor and pain reducing inflammation via cannabinoid-mediated system. The aim of our study is to investigate the changes in cannabinoid type 1 (CNR1) and 2 (CNR2) receptors mRNA expression levels and promoter methylation in peripheral blood mononuclear cells (PBMCs) of MS secondary progressive (MSS-SP) patients treated with Sativex®...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28534260/pharmacogenetics-of-cannabinoids
#11
Szymon Hryhorowicz, Michal Walczak, Oliwia Zakerska-Banaszak, Ryszard Słomski, Marzena Skrzypczak-Zielińska
Although the application of medical marijuana and cannabinoid drugs is controversial, it is a part of modern-day medicine. The list of diseases in which cannabinoids are promoted as a treatment is constantly expanding. Cases of significant improvement in patients with a very poor prognosis of glioma or epilepsy have already been described. However, the occurrence of side effects is still difficult to estimate, and the current knowledge of the therapeutic effects of cannabinoids is still insufficient. In our opinion, the answers to many questions and concerns regarding the medical use of cannabis can be provided by pharmacogenetics...
May 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28481838/contribution-of-endocannabinoid-gene-expression-and-genotype-on-low-back-pain-susceptibility-and-chronicity
#12
Divya Ramesh, Amy D'Agata, Angela Starkweather, Erin Young
A major research emphasis has been focused on defining the molecular changes that occur from acute to chronic pain in order to identify potential therapeutic targets for chronic pain. As the endocannabinoid system is dynamically involved in pain signaling, a plausible mechanism that may contribute to chronic pain vulnerability involves alterations in the amount of circulating endocannabinoids. Therefore, this study sought to examine cannabinoid type-1 (CNR1), type-2 (CNR2) receptors, fatty acid amide hydrolase (FAAH) and the vanilloid receptor (TRPV1) gene expression profiles among individuals with acute and chronic LBP at their baseline visit...
May 5, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28349993/cannabinoid-receptor-type-1-and-mu-opioid-receptor-polymorphisms-are-associated-with-cyclic-vomiting-syndrome
#13
Andrzej Wasilewski, Urszula Lewandowska, Paula Mosinska, Cezary Watala, Martin Storr, Jakub Fichna, Thangam Venkatesan
OBJECTIVES: Cyclic vomiting syndrome (CVS) is a disorder defined by recurrent, unexplained episodes of severe nausea and vomiting. Our aim was to investigate whether CVS and pathophysiological mechanisms underlying this condition are associated with selected variations in genes encoding the components of the endogenous cannabinoid and opioid systems. METHODS: This case-control study included 65 patients with CVS-16 male and 49 female, and 1,092 healthy controls-525 male and 567 female from the 1000 Genomes Project...
June 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28332672/formation-of-paramagnetic-metallacyclobutadienes-by-reaction-of-diaminoacetylenes-with-molybdenum-alkylidyne-complexes
#14
Òscar Àrias, Kai Brandhorst, Dirk Baabe, Matthias Freytag, Peter G Jones, Matthias Tamm
The reactions of the molybdenum alkylidyne complex [MesC[triple bond, length as m-dash]Mo{OCMe(CF3)2}3] (1) with the diaminoacetylenes R2NC[triple bond, length as m-dash]CNR2 (2, NR2 = 4-methylpiperidinyl; 3, NR2 = NEt2; Mes = 2,4,6-trimethylphenyl) afforded the metallacyclobutadiene (MCBD) complexes 4 and 5. In contrast to all other MCBD complexes, 4 and 5 are paramagnetic and best described as Mo(iv) species containing an anionic diaminodicarbene of the type [(R2N)CC(Mes)C(NR2)](-).
March 23, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28283967/exercise-training-and-high-fat-diet-elicit-endocannabinoid-system-modifications-in-the-rat-hypothalamus-and-hippocampus
#15
François-Xavier Gamelin, Julien Aucouturier, Fabio Arturo Iannotti, Fabiana Piscitelli, Enrico Mazzarella, Teresa Aveta, Melissa Leriche, Erwan Dupont, Caroline Cieniewski-Bernard, Erwan Leclair, Bruno Bastide, Vincenzo Di Marzo, Elsa Heyman
The purpose of the present study was to examine the effect of chronic exercise on the hypothalamus and hippocampus levels of the endocannabinoids (eCBs) anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and of two AEA congeners and on the expression of genes coding for CB1, CB2 receptors (Cnr1 and Cnr2, respectively), and the enzymes responsible for eCB biosynthesis and degradation, in rats fed with a standard or high-fat diet. Male Wistar rats (n = 28) were placed on a 12-week high-fat (HFD) or standard diet period, followed by 12 weeks of exercise training for half of each group...
August 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28274851/emerging-therapeutic-targets-in-cancer-induced-bone-disease-a-focus-on-the-peripheral-type-2-cannabinoid-receptor
#16
REVIEW
Silvia Marino, Aymen I Idris
Skeletal complications are a common cause of morbidity in patients with primary bone cancer and bone metastases. The type 2 cannabinoid (Cnr2) receptor is implicated in cancer, bone metabolism and pain perception. Emerging data have uncovered the role of Cnr2 in the regulation of tumour-bone cell interactions and suggest that agents that target Cnr2 in the skeleton have potential efficacy in the reduction of skeletal complications associated with cancer. This review aims to provide an overview of findings relating to the role of Cnr2 receptor in the regulation of skeletal tumour growth, osteolysis and bone pain, and highlights the many unanswered questions and unmet needs...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28192788/metabolic-gatekeeper-function-of-b-lymphoid-transcription-factors
#17
Lai N Chan, Zhengshan Chen, Daniel Braas, Jae-Woong Lee, Gang Xiao, Huimin Geng, Kadriye Nehir Cosgun, Christian Hurtz, Seyedmehdi Shojaee, Valeria Cazzaniga, Hilde Schjerven, Thomas Ernst, Andreas Hochhaus, Steven M Kornblau, Marina Konopleva, Miles A Pufall, Giovanni Cazzaniga, Grace J Liu, Thomas A Milne, H Phillip Koeffler, Theodora S Ross, Isidro Sánchez-García, Arndt Borkhardt, Keith R Yamamoto, Ross A Dickins, Thomas G Graeber, Markus Müschen
B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply...
February 23, 2017: Nature
https://www.readbyqxmd.com/read/27920729/transcriptional-network-architecture-of-breast-cancer-molecular-subtypes
#18
Guillermo de Anda-Jáuregui, Tadeo E Velázquez-Caldelas, Jesús Espinal-Enríquez, Enrique Hernández-Lemus
Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27734700/-the-endocannabinoid-system-and-bone
#19
Mikuláš Pura, Peter Vaňuga
Recent studies suggest an important role for the skeletal endocannabinoid system in the regulation of bone mass in both physiological and pathological conditions. Both major endocannabinoids (anandamid and 2-arachidonoylglycerol), endocannabinoid receptors - CB1-receptor (CB1R) a CB2-receptor (CB2R) and the endocannabinoid metabolizing enzymes are present or expressed in osteoblasts and osteoclasts. Previous studies identified multiple risk and protective variants of CNR2 gene dealing with the relationship to bone density and/or osteoporosis...
December 0: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27476469/cb2-63-polymorphism-and-immune-mediated-diseases-associated-with-hcv-chronic-infection
#20
Nicola Coppola, Rosa Zampino, Giulia Bellini, Maria Stanzione, Nicolina Capoluongo, Aldo Marrone, Margherita Macera, Luigi Elio Adinolfi, Emanuele Miraglia Del Giudice, Ivan Gentile, Evangelista Sagnelli, Francesca Rossi
AIMS: To evaluate whether CB2 variants are associated with the presence of immune-mediated disorders (IMDs) in patients with chronic HCV infection. METHODS: One hundred and sixty-eight anti-HCV/HCV-RNA-positive patients were enrolled, 81 with signs of IMDs and 87 without. In the IMDs group, 22 (27.2%) showed ANA positivity (titers ≥1:160), 3 (3.7%) SMA positivity (titers ≥1:160), 24 (29.6%) had cryoglobulinemia, 25 (30.9%) autoimmune thyroiditis, 4 (4.9%) psoriasis, 2 (2...
November 2016: Digestive and Liver Disease
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