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Endocannabinoid deficiency

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https://www.readbyqxmd.com/read/29274505/age-related-regulation-of-bone-formation-by-the-sympathetic-cannabinoid-cb1-receptor
#1
Saif Deis, Raj Kamal Srivastava, Inigo Ruiz de Azua, Laura Bindila, Saja Baraghithy, Beat Lutz, Itai Bab, Joseph Tam
The endocannabinoid (eCB) system, including its receptors, ligands, and their metabolizing enzymes, plays an important role in bone physiology. Skeletal cannabinoid type 1 (CB1) receptor signaling transmits retrograde signals that restrain norepinephrine (NE) release, thus transiently stimulating bone formation following an acute challenge, suggesting a feedback circuit between sympathetic nerve terminals and osteoblasts. To assess the effect of chronic in vivo occurrence of this circuit, we characterized the skeletal phenotype of mice with a conditional deletion of the CB1 receptor in adrenergic/noradrenergic cells, including sympathetic nerves...
December 20, 2017: Bone
https://www.readbyqxmd.com/read/29167401/acetaminophen-relieves-inflammatory-pain-through-cb1-cannabinoid-receptors-in-the-rostral-ventromedial-medulla
#2
Pascal P Klinger-Gratz, William T Ralvenius, Elena Neumann, Ako Kato, Rita Nyilas, Zsolt Lele, István Katona, Hanns Ulrich Zeilhofer
Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug with only incompletely understood mechanisms of action. Previous work, using models of acute nociceptive pain, indicated that analgesia by acetaminophen involves an indirect activation of CB1 receptors by the acetaminophen metabolite and endocannabinoid re-uptake inhibitor AM 404. However, the contribution of the cannabinoid system to anti-hyperalgesia against inflammatory pain, the main indication of acetaminophen, and the precise site of the relevant CB1 receptors have remained elusive...
November 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29145497/rare-genetic-variants-in-the-endocannabinoid-system-genes-cnr1-and-dagla-are-associated-with-neurological-phenotypes-in-humans
#3
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/29068398/precision-nutrition-and-omega-3-polyunsaturated-fatty-acids-a-case-for-personalized-supplementation-approaches-for-the-prevention-and-management-of-human-diseases
#4
REVIEW
Floyd H Chilton, Rahul Dutta, Lindsay M Reynolds, Susan Sergeant, Rasika A Mathias, Michael C Seeds
BACKGROUND: Dietary essential omega-6 (n-6) and omega-3 (n-3) 18 carbon (18C-) polyunsaturated fatty acids (PUFA), linoleic acid (LA) and α-linolenic acid (ALA), can be converted (utilizing desaturase and elongase enzymes encoded by FADS and ELOVL genes) to biologically-active long chain (LC; >20)-PUFAs by numerous cells and tissues. These n-6 and n-3 LC-PUFAs and their metabolites (ex, eicosanoids and endocannabinoids) play critical signaling and structural roles in almost all physiologic and pathophysiologic processes...
October 25, 2017: Nutrients
https://www.readbyqxmd.com/read/29031713/peripheral-cannabinoid-1-receptor-blockade-restores-hypothalamic-leptin-signaling
#5
Joseph Tam, Gergő Szanda, Adi Drori, Ziyi Liu, Resat Cinar, Yoshihiro Kashiwaya, Marc L Reitman, George Kunos
OBJECTIVE: In visceral obesity, an overactive endocannabinoid/CB1 receptor (CB1R) system promotes increased caloric intake and decreases energy expenditure, which are mitigated by global or peripheral CB1R blockade. In mice with diet-induced obesity (DIO), inhibition of food intake by the peripherally restricted CB1R antagonist JD5037 could be attributed to endogenous leptin due to the rapid reversal of hyperleptinemia that maintains leptin resistance, but the signaling pathway engaged by leptin has remained to be determined...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28852269/cannabinoid-receptor-2-modulates-neutrophil-recruitment-in-a-murine-model-of-endotoxemia
#6
Theodore S Kapellos, Carlota Recio, David R Greaves, Asif J Iqbal
The endocannabinoid system consists of endogenous lipid mediators and cannabinoid receptors (CB) 1 and 2. It has previously been demonstrated that activation of the leukocyte-expressed CB2 has anti-inflammatory effects in vivo. Here, we report its role under baseline conditions and in a model of low-dose endotoxemia by comparing CB2 knockout to littermate control mice. CB2-deficient mice displayed significantly more neutrophils and fewer monocytes in the bone marrow under steady state. In initial validation experiments, administration of 1 mg/kg LPS to male C57BL/6J mice was shown to transiently upregulate systemic proinflammatory mediators (peaked at 2 hours) and mobilise bone marrow neutrophils and monocytes into circulation...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28799288/neuroprotective-activity-of-cannabinoid-receptor-2-against-oxidative-stress-and-apoptosis-in-rat-pups-having-experimentally-induced-congenital-hypothyroidism
#7
Mehmet Eray Alcigir, Halef Okan Dogan, Sevil Atalay Vural, Fatma Meric Yilmaz
In this study, it was aimed to show the cannabinoid receptor-2 (CB2) role, which is a part of neuroprotective endocannabinoidal system, against increasing nitric oxide synthetase (iNOS, eNOS) levels and the apoptotic activity (caspase-3, caspase-9, and DNA in situ fragmentation) within the postnatal critical period in pups of pregnant rats with artificially induced maternal thyroid hormone (TH) deficiency. Each of the three groups established comprised one male and two female rats, and they were coupled. Their pups were used...
August 11, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28759733/protective-effect-of-rimonabant-a-canabinoid-receptor-1-antagonist-on-nonalcoholic-fatty-liver-disease-in-a-rat-model-through-modulation-of-the-hepatic-expression-of-activin-a-and-follistatin
#8
Noha I Hussien, Hanan I El-Kerdasy, Mohammad El-Tantawy Ibrahim
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality, and there is still no proven effective therapy. The endocannabinoid system plays an important role in various liver diseases. Activin A is a member of the transforming growth factor beta (TGF-β) superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin A. This study was designed to investigate the effect of rimonabant (a potent cannabinoid receptor1 (CB1) antagonist) on NAFLD induced with a choline-deficient (CD) diet in rats, as well as to detect whether it can alter the hepatic expression of activin A and follistatin...
July 31, 2017: Canadian Journal of Physiology and Pharmacology
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/28745306/integrating-endocannabinoid-signaling-and-cannabinoids-into-the-biology-and-treatment-of-posttraumatic-stress-disorder
#10
Matthew N Hill, Patrizia Campolongo, Rachel Yehuda, Sachin Patel
Exposure to stress is an undeniable, but in most cases surmountable, part of life. However, in certain individuals, exposure to severe or cumulative stressors can lead to an array of pathological conditions including posttraumatic stress disorder (PTSD), characterized by debilitating trauma-related intrusive thoughts, avoidance behaviors, hyperarousal, as well as depressed mood and anxiety. In the context of the rapidly changing political and legal landscape surrounding use of cannabis products in the United States, there has been a surge of public and research interest in the role of cannabinoids in the regulation of stress-related biological processes and in their potential therapeutic application for stress-related psychopathology...
July 26, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28630250/amplification-of-mglu5-endocannabinoid-signaling-rescues-behavioral-and-synaptic-deficits-in-a-mouse-model-of-adolescent-and-adult-dietary-polyunsaturated-fatty-acid-imbalance
#11
Antonia Manduca, Anissa Bara, Thomas Larrieu, Olivier Lassalle, Corinne Joffre, Sophie Layé, Olivier J Manzoni
Energy-dense, yet nutritionally poor food is a high-risk factor for mental health disorders. This is of particular concern during adolescence, a period often associated with increased consumption of low nutritional content food and higher prevalence of mental health disorders. Indeed, there is an urgent need to understand the mechanisms linking unhealthy diet and mental disorders. Deficiency in n-3 polyunsaturated fatty acids (PUFAs) is a hallmark of poor nutrition and mood disorders. Here, we developed a mouse model of n-3 PUFA deficiency lasting from adolescence into adulthood...
July 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28515018/plasma-levels-of-the-endocannabinoid-anandamide-related-n-acylethanolamines-and-linoleic-acid-derived-oxylipins-in-patients-with-migraine
#12
Sandra Gouveia-Figueira, Kristina Goldin, Sanaz A Hashemian, Agneta Lindberg, Monica Persson, Malin L Nording, Katarina Laurell, Christopher J Fowler
There is evidence that patients with migraine have deficient levels of the endogenous cannabinoid receptor ligand anandamide (AEA). It is not known, however, if this is a localised or generalised phenomenon. In the present study, levels of AEA, related N-acylethanolamines (NAEs) and linoleic acid-derived oxylipins have been measured in the blood of 26 healthy women and 38 women with migraine (26 with aura, 12 without aura) who were matched for age and body-mass index. Blood samples were taken on two occasions: the first sample near the start of the menstrual cycle (when present) and the second approximately fourteen days later...
May 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28438413/functional-redundancy-between-canonical-endocannabinoid-signaling-systems-in-the-modulation-of-anxiety
#13
Gaurav Bedse, Nolan D Hartley, Emily Neale, Andrew D Gaulden, Toni A Patrick, Philip J Kingsley, Md Jashim Uddin, Niels Plath, Lawrence J Marnett, Sachin Patel
BACKGROUND: Increasing the available repertoire of effective treatments for mood and anxiety disorders represents a critical unmet need. Pharmacological augmentation of endogenous cannabinoid (eCB) signaling has been suggested to represent a novel approach to the treatment of anxiety disorders; however, the functional interactions between two canonical eCB pathways mediated via anandamide (N-arachidonylethanolamine [AEA]) and 2-arachidonoylglycerol (2-AG) in the regulation of anxiety are not well understood...
October 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28380440/monoglyceride-lipase-deficiency-affects-hepatic-cholesterol-metabolism-and-lipid-dependent-gut-transit-in-apoe-mice
#14
Nemanja Vujic, Melanie Korbelius, Christina Leopold, Madalina Duta-Mare, Silvia Rainer, Stefanie Schlager, Madeleine Goeritzer, Dagmar Kolb, Thomas O Eichmann, Clemens Diwoky, Andreas Zimmer, Robert Zimmermann, Achim Lass, Branislav Radovic, Dagmar Kratky
Monoglyceride lipase (MGL) hydrolyzes monoglycerides (MGs) to glycerol and fatty acids. Among various MG species MGL also degrades 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid and potent activator of cannabinoid receptors (CBR) 1 and 2. MGL-knockout (-/-) mice exhibit pronounced 2-AG accumulation, but lack central cannabimimetic effects due to CB1R desensitization. We have previously shown that MGL affects plaque stability in apolipoprotein E (ApoE)-/- mice, an established animal model for dyslipidemia and atherosclerosis...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28373843/antihyperalgesic-activities-of-endocannabinoids-in-a-mouse-model-of-antiretroviral-induced-neuropathic-pain
#15
Neha Munawar, Mabayoje A Oriowo, Willias Masocha
Background: Nucleoside reverse transcriptase inhibitors (NRTIs) are the cornerstone of the antiretroviral therapy for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). However, their use is sometimes limited by the development of a painful sensory neuropathy, which does not respond well to drugs. Smoked cannabis has been reported in clinical trials to have efficacy in relieving painful HIV-associated sensory neuropathy. Objectives: The aim of this study was to evaluate whether the expression of endocannabinoid system molecules is altered during NRTI-induced painful neuropathy, and also whether endocannabinoids can attenuate NRTI-induced painful neuropathy...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28254386/the-role-of-exercise-training-and-the-endocannabinoid-system-in-atherosclerotic-plaque-burden-and-composition-in-apo-e-deficient-mice
#16
Michalis Katsimpoulas, Nikolaos E Kadoglou, Petros Moustardas, Alkistis Kapelouzou, Eleni Dede, Nikolaos Kostomitsopoulos, Panayotis E Karayannacos, Alkiviadis Kostakis, Christos D Liapis
INTRODUCTION: We investigated the effect of combining exercise training and treatment with an endocannabinoid receptor 1 inhibitor (Rimonabant) on atherosclerosis burden and composition. METHODS: Forty-eight apolipoprotein E-deficient (ApoE-/-) mice were kept on a 16-week high-fat diet. Mice were then placed on a normal diet and were randomized to the following groups with n=12 mice for 6 more weeks: 1) Control (Co) - no intervention; 2) Exercise (Ex) - exercise training on treadmill; 3) Rimonabant (Ri) - oral administration of rimonabant (10 mg/kg/day); or 4) Rimonabant+Exercise (RiEx) - combination of Ri and Ex groups treatment...
November 2016: Hellenic Journal of Cardiology: HJC, Hellēnikē Kardiologikē Epitheōrēsē
https://www.readbyqxmd.com/read/28079617/manipulation-of-the-endocannabinoid-system-in-colitis-a-comprehensive-review
#17
Kristina L Leinwand, Mark E Gerich, Edward J Hoffenberg, Colm B Collins
BACKGROUND: Inflammatory bowel disease (IBD) is a lifelong disease of the gastrointestinal tract whose annual incidence and prevalence is on the rise. Current immunosuppressive therapies available for treatment of IBD offer limited benefits and lose effectiveness, exposing a significant need for the development of novel therapies. In the clinical setting, cannabis has been shown to provide patients with IBD symptomatic relief, although the underlying mechanisms of their anti-inflammatory effects remain unclear...
February 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27959272/fetal-syndrome-of-endocannabinoid-deficiency-fsecd-in-maternal-obesity
#18
Natalia Schlabritz-Loutsevitch, Nadezhda German, Gary Ventolini, Eneko Larumbe, Jacques Samson
The theory of a fetal origin of adult diseases links many pathological conditions to very early life events and is known as a "developmental programming" phenomenon. The mechanisms of this phenomenon are not quite understood and have been explained by inflammation, stress, etc. In particular the epidemic of obesity, with more than 64% of women being overweight or obese, has been associated with conditions in later life such as mental disorders, diabetes, asthma, and irritable bowel syndrome. Interestingly, these diseases were classified a decade ago as Clinical Syndrome of Endocannabinoid Deficiency (CECD), which was first described by Russo in 2004...
November 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27903595/lifelong-imbalanced-la-ala-intake-impairs-emotional-and-cognitive-behavior-via-changes-in-brain-endocannabinoid-system
#19
Erica Zamberletti, Fabiana Piscitelli, Valentina De Castro, Elisabetta Murru, Marina Gabaglio, Paola Colucci, Chiara Fanali, Pamela Prini, Tiziana Bisogno, Mauro Maccarrone, Patrizia Campolongo, Sebastiano Banni, Tiziana Rubino, Daniela Parolaro
Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system appears to be an ideal candidate for mediating the effects of dietary fatty acids on mood and cognition. Lifelong administration of isocaloric α-linolenic acid (ALA)-deficient and -enriched diets induced short-term memory deficits, whereas only dietary ALA enrichment altered emotional reactivity in adult male rats compared with animals fed a standard diet that was balanced in ALA/linoleic acid (LA) ratio...
February 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/27698427/cannabinoid-cb1-receptors-in-distinct-circuits-of-the-extended-amygdala-determine-fear-responsiveness-to-unpredictable-threat
#20
M D Lange, T Daldrup, F Remmers, H J Szkudlarek, J Lesting, S Guggenhuber, S Ruehle, K Jüngling, T Seidenbecher, B Lutz, H C Pape
The brain circuits underlying behavioral fear have been extensively studied over the last decades. Although the vast majority of experimental studies assess fear as a transient state of apprehension in response to a discrete threat, such phasic states of fear can shift to a sustained anxious apprehension, particularly in face of diffuse cues with unpredictable environmental contingencies. Unpredictability, in turn, is considered an important variable contributing to anxiety disorders. The networks of the extended amygdala have been suggested keys to the control of phasic and sustained states of fear, although the underlying synaptic pathways and mechanisms remain poorly understood...
October 2017: Molecular Psychiatry
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