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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/29107297/decreasing-cb1-receptor-signaling-in-kupffer-cells-improves-insulin-sensitivity-in-obese-mice
#2
Tony Jourdan, Sarah M Nicoloro, Zhou Zhou, Yuefei Shen, Jie Liu, Nathan J Coffey, Resat Cinar, Grzegorz Godlewski, Bin Gao, Myriam Aouadi, Michael P Czech, George Kunos
OBJECTIVE: Obesity-induced accumulation of ectopic fat in the liver is thought to contribute to the development of insulin resistance, and increased activity of hepatic CB1R has been shown to promote both processes. However, lipid accumulation in liver can be experimentally dissociated from insulin resistance under certain conditions, suggesting the involvement of additional mechanisms. Obesity is also associated with pro-inflammatory changes which, in turn, can promote insulin resistance...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29106063/cannabinoid-1-receptor-deletion-in-podocytes-mitigates-both-glomerular-and-tubular-dysfunction-in-a-mouse-model-of-diabetic-nephropathy
#3
Tony Jourdan, Joshua K Park, Zoltán V Varga, János Pálóczi, Nathan J Coffey, Avi Z Rosenberg, Grzegorz Godlewski, Resat Cinar, Ken Mackie, Pal Pacher, George Kunos
AIMS: To determine the specific role of podocyte-expressed cannabinoid-1 receptor (CB1 R) in the development of diabetic nephropathy (DN), relative to CB1 R in other renal cell types. MATERIAL AND METHODS: We developed a mouse model with a podocyte-specific deletion of CB1 R (pCB1Rko) and challenged this model with streptozotocin (STZ)-induced type-1 DN. We also assessed the podocyte response to high glucose in vitro and its effects on CB1 R activation. RESULTS: High glucose exposure for 48h led to an increase in CB1 R gene expression (CNR1) and endocannabinoid production in cultured human podocytes...
November 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29105060/cannabinoid-receptor-1-2-double-knockout-mice-develop-epilepsy
#4
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/29093492/the-association-between-gene-variants-and-longitudinal-structural-brain-changes-in-psychosis-a-systematic-review-of-longitudinal-neuroimaging-genetics-studies
#5
REVIEW
Julia H Harari, Covadonga M Díaz-Caneja, Joost Janssen, Kenia Martínez, Bárbara Arias, Celso Arango
Evidence suggests that genetic variation might influence structural brain alterations in psychotic disorders. Longitudinal genetic neuroimaging (G-NI) studies are designed to assess the association between genetic variants, disease progression and brain changes. There is a paucity of reviews of longitudinal G-NI studies in psychotic disorders. A systematic search of PubMed from inception until November 2016 was conducted to identify longitudinal G-NI studies examining the link between Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI)-based brain measurements and specific gene variants (SNPs, microsatellites, haplotypes) in patients with psychosis...
November 1, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/29082317/cannabinoid-receptor-1-gene-by-cannabis-use-interaction-on-cb1-receptor-density
#6
Ariel Ketcherside, Lindsey J Noble, Christa K McIntyre, Francesca M Filbey
Background: Because delta-9-tetrahydrocannabinol (THC), the primary psychoactive ingredient in cannabis, binds to cannabinoid 1 (CB1) receptors, levels of CB1 protein could serve as a potential biomarker for response to THC. To date, available techniques to characterize CB1 expression and function in vivo are limited. In this study, we developed an assay to quantify CB1 in lymphocytes to determine how it relates to cannabis use in 58 daily cannabis users compared with 47 nonusers. Furthermore, we tested whether CB1 levels are associated with mutations in a single nucleotide polymorphism known to regulate CB1 functioning (i...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29065845/identification-of-electrophysiological-changes-in-alzheimer-s-disease-a-microarray-based-transcriptomics-and-molecular-pathway-analysis-study
#7
Zeenat Mirza, Nisreen Rajeh
Involvement of amyloid beta and tau proteins in pathogenesis of Alzheimer's disease (AD) has been studied extensively. However, electrophysiological activity, and cellular processes like membrane transport are mostly unstudied. Electrophysiological processes provide a bridge between brain activity and cognition, and show promise as translatable biomarkers in preclinical and clinical applications. Biochemical imbalance leads to change in glutamate-based neurotransmission, antioxidant capacity, and in membrane polarization-repolarization events, eventually, resulting in AD...
October 23, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29021832/pharmacogenomics-in-the-treatment-of-mood-disorders-strategies-and-opportunities-for-personalized-psychiatry
#8
REVIEW
Azmeraw T Amare, Klaus Oliver Schubert, Bernhard T Baune
Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/28930056/developmentally-specific-associations-between-cnr1-genotype-and-cannabis-use-across-emerging-adulthood
#9
James R Ashenhurst, K Paige Harden, Travis T Mallard, William R Corbin, Kim Fromme
OBJECTIVE: Previous studies have found preliminary evidence for associations between common single-nucleotide polymorphisms (SNPs) in the cannabinoid receptor gene CNR1 and cannabis use and dependence. The present study examined a set of eight independent SNPs in or near CNR1 in relation to cannabis use measured longitudinally across emerging adulthood. METHOD: Using latent growth curve modeling of 10 waves of longitudinal data spanning mean ages 18.4-23.8 years in a sample of non-Hispanic White individuals (n = 334), we tested if genotype at each CNR1 SNP was associated with both level and growth of cannabis use over time...
September 2017: Journal of Studies on Alcohol and Drugs
https://www.readbyqxmd.com/read/28880852/rna-sequencing-uncovers-molecular-mechanisms-underlying-pathological-complete-response-to-chemotherapy-in-patients-with-operable-breast-cancer
#10
Yongfeng Li, Xiaozhen Liu, Hongchao Tang, Hongjian Yang, Xuli Meng
BACKGROUND This study aimed to identify key genes contributing to pathological complete response (pCR) to chemotherapy by mRNA sequencing (RNA-seq). MATERIAL AND METHODS RNA was extracted from the frozen biopsy tissue of patients with pathological complete response and patients with non-pathological complete response. Sequencing was performed on the HiSeq2000 platform. Differentially expressed genes (DEGs) were identified between the pCR group and non-pCR (NpCR) group. Pathway enrichment analysis of DEGs was performed...
September 7, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28875496/g-protein-coupled-receptor-gpr55-promotes-colorectal-cancer-and-has-opposing-effects-to-cannabinoid-receptor-1
#11
Carina Hasenoehrl, David Feuersinger, Eva M Sturm, Thomas Bärnthaler, Ellen Heitzer, Ricarda Graf, Magdalena Grill, Martin Pichler, Stephan Beck, Lee Butcher, Dominique Thomas, Nerea Ferreirós, Rufina Schuligoi, Caroline Schweiger, Johannes Haybaeck, Rudolf Schicho
The putative cannabinoid receptor GPR55 has been shown to play a tumor-promoting role in various cancers, and is involved in many physiological and pathological processes of the gastrointestinal (GI) tract. While the cannabinoid receptor 1 (CB1 ) has been reported to suppress intestinal tumor growth, the role of GPR55 in the development of GI cancers is unclear. We, therefore, aimed at elucidating the role of GPR55 in colorectal cancer (CRC), the third most common cancer worldwide. Using azoxymethane (AOM)- and dextran sulfate sodium (DSS)-driven CRC mouse models, we found that GPR55 plays a tumor-promoting role that involves alterations of leukocyte populations, i...
January 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28837063/daytime-dependent-changes-of-cannabinoid-receptor-type-1-and-type-2-expression-in-rat-liver
#12
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/28774834/role-of-forkhead-box-class-o-proteins-in-cancer-progression-and-metastasis
#13
REVIEW
Chang Geun Kim, Hyemin Lee, Nehal Gupta, Sharavan Ramachandran, Itishree Kaushik, Sangeeta Srivastava, Sung-Hoon Kim, Sanjay K Srivastava
It is now widely accepted that several gene alterations including transcription factors are critically involved in cancer progression and metastasis. Forkhead Box Class O proteins (FoxOs) including FoxO1/FKHR, FoxO3/FKHRL1, FoxO4/AFX and FoxO6 transcription factors are known to play key roles in proliferation, apoptosis, metastasis, cell metabolism, aging and cancer biology through their phosphorylation, ubiquitination, acetylation and methylation. Though FoxOs are proved to be mainly regulated by upstream phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway, the role of FoxOs in cancer progression and metastasis still remains unclear so far...
August 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28766743/mouse-retinal-ganglion-cell-signalling-is-dynamically-modulated-through-parallel-anterograde-activation-of-cannabinoid-and-vanilloid-pathways
#14
Andrew O Jo, Jennifer M Noel, Monika Lakk, Oleg Yarishkin, Daniel A Ryskamp, Koji Shibasaki, Maureen A McCall, David Križaj
KEY POINTS: Retinal cells use vanilloid transient receptor potential (TRP) channels to integrate light-evoked signals with ambient mechanical, chemical and temperature information. Localization and function of the polymodal non-selective cation channel TRPV1 (transient receptor potential vanilloid isoform 1) remains elusive. TRPV1 is expressed in a subset of mouse retinal ganglion cells (RGCs) with peak expression in the mid-peripheral retina. Endocannabinoids directly activate TRPV1 and inhibit it through cannabinoid type 1 receptors (CB1Rs) and cAMP pathways...
October 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28752643/combined-deficiency-of-the-cnr1-and-cnr2-receptors-protects-against-age-related-bone-loss-by-osteoclast-inhibition
#15
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
#16
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/28687732/the-cannabinoid-receptor-interacting-proteins-1-of-zebrafish-are-not-required-for-morphological-development-viability-or-fertility
#17
Laura Fin, Giorgia Bergamin, Roberto A Steiner, Simon M Hughes
The Cannabinoid Receptor Interacting Protein 1 (Cnrip1) was discovered as an interactor with the intracellular region of Cannabinoid Receptor 1 (CB1R, also known as Cnr1 or CB1). Functional assays in mouse show cannabinoid sensitivity changes and Cnrip1 has recently been suggested to control eye development in Xenopus laevis. Two Cnrip1 genes are described in zebrafish, cnrip1a and cnrip1b. In situ mRNA hybridisation revealed accumulation of mRNA encoding each gene primarily in brain and spinal cord, but also elsewhere...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28685667/a-variant-on-promoter-of-the-cannabinoid-receptor-1-gene-cnr1-moderates-the-effect-of-valence-on-working-memory
#18
Beth Fairfield, Nicola Mammarella, Marica Franzago, Alberto Di Domenico, Liborio Stuppia, Valentina Gatta
Cannabinoid receptor 1 gene (CNR1) variants have been related to affective information processing and, in particular, to stress release. Here, we aimed to examine whether the endocannabinoid system via CNR1 signaling modulates affective working memory, the memory system that transiently maintains and manipulates emotionally charged material. We focused on rs2180619 (A > G) polymorphism and examined genotype data collected from 231 healthy females. Analyses showed how a general positivity bias in working memory (i...
July 7, 2017: Memory
https://www.readbyqxmd.com/read/28534260/pharmacogenetics-of-cannabinoids
#19
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
#20
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
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