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Endocannabinoid

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https://www.readbyqxmd.com/read/28726298/faah-but-not-magl-inhibition-modulates-acute-tlr3-induced-neuroimmune-signaling-in-the-rat-independent-of-sex
#1
Lisa E Flannery, Rebecca J Henry, Daniel M Kerr, David P Finn, Michelle Roche
Toll-like receptor (TLR)3 is a key component of the innate immune response to viral infection. The present study firstly examined whether sex differences exist in TLR3-induced inflammatory, endocrine, and sickness responses. The data revealed that TLR3-induced expression of interferon- or NFkB-inducible genes (IFN-α/β, IP-10, or TNF-α), either peripherally (spleen) or centrally (hypothalamus), did not differ between male and female rats, with the exception of TLR3-induced IFN-α expression in the spleen of female, but not male, rats 8 hr post TLR3 activation...
July 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28724917/endocannabinoids-have-opposing-effects-on-behavioral-responses-to-nociceptive-and-non-nociceptive-stimuli
#2
Torrie Summers, Brandon Hanten, Warren Peterson, Brian Burrell
The endocannabinoid system is thought to modulate nociceptive signaling making it a potential therapeutic target for treating pain. However, there is evidence that endocannabinoids have both pro- and anti-nociceptive effects. In previous studies using Hirudo verbana (the medicinal leech), endocannabinoids were found to depress nociceptive synapses, but enhance non-nociceptive synapses. Here we examined whether endocannabinoids have similar bidirectional effects on behavioral responses to nociceptive vs. non-nociceptive stimuli in vivo...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716633/the-synthetic-cannabinoid-win55212-2-ameliorates-traumatic-spinal-cord-injury-via-inhibition-of-gapdh-siah1-in-a-cb2-receptor-dependent-manner
#3
Bin-Xiao Su, Xin Chen, Jia Huo, Shu-Yun Guo, Rui Ma, Yan-Wu Liu
The essential role of GAPDH/Siah1 signaling pathway in the pathogenesis of various injurious conditions such as traumatic spinal cord injury (SCI) has been gradually recognized. However, the drugs targeting this signaling pathway are still lacking. The endocannabinoid system, including its receptors (CB1 and CB2), act as neuroprotective and immunomodulatory modulators in SCI. WIN55212-2, an agonist for CB1 and CB2 receptors, has been demonstrated with anti-inflammatory and anti-apoptotic effects in multiple neurological diseases...
July 14, 2017: Brain Research
https://www.readbyqxmd.com/read/28705172/endocannabinoid-receptor-blockade-reduces-alanine-aminotransferase-in-polycystic-ovary-syndrome-independent-of-weight-loss
#4
Alison J Dawson, Eric S Kilpatrick, Anne-Marie Coady, Abeer M M Elshewehy, Youssra Dakroury, Lina Ahmed, Stephen L Atkin, Thozhukat Sathyapalan
BACKGROUND: Evidence suggests that endocannabinoid system activation through the cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1 antagonism may be beneficial. The aim of this study was to determine the impact of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a hepatocellular injury marker, and a hepatic inflammatory cytokine profile. METHODS: Post hoc review of 2 studies involving 50 obese women with PCOS and well matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od) or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg tds), or pioglitazone (45 mg od)...
July 14, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28704272/epigenetic-mechanisms-associated-with-addiction-related-behavioural-effects-of-nicotine-and-or-cocaine-implication-of-the-endocannabinoid-system
#5
Tamaki Hayase
The addictive use of nicotine (NC) and cocaine (COC) continues to be a major public health problem, and their combined use has been reported, particularly during adolescence. In neural plasticity, commonly induced by NC and COC, as well as behavioural plasticity related to the use of these two drugs, the involvement of epigenetic mechanisms, in which the reversible regulation of gene expression occurs independently of the DNA sequence, has recently been reported. Furthermore, on the basis of intense interactions with the target neurotransmitter systems, the endocannabinoid (ECB) system has been considered pivotal for eliciting the effects of NC or COC...
July 12, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28700932/selectively-impaired-endocannabinoid-dependent-long-term-depression-in-the-lateral-habenula-in-an-animal-model-of-depression
#6
Hoyong Park, Jeehae Rhee, Seongju Lee, ChiHye Chung
Abnormal potentiation in the lateral habenula (LHb) has been suggested to mediate depression-like behaviors. However, the underlying mechanisms of the synaptic efficacy regulation of LHb synapses and the potential for their modulation are only poorly understood. Here, we report that long-term synaptic depression (LTD) occurs in the LHb upon both low-frequency stimulation (LFS) and moderate-frequency stimulation (MFS). LFS-induced LTD (LFS-LTD) is accompanied by a reduction in presynaptic release probability, which is endocannabinoid (eCB) signaling dependent...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28700706/spatial-distribution-of-cannabinoid-receptor-type-1-cb1-in-normal-canine-central-and-peripheral-nervous-system
#7
Jessica Freundt-Revilla, Kristel Kegler, Wolfgang Baumgärtner, Andrea Tipold
The endocannabinoid system is a regulatory pathway consisting of two main types of cannabinoid receptors (CB1 and CB2) and their endogenous ligands, the endocannabinoids. The CB1 receptor is highly expressed in the central and peripheral nervous systems (PNS) in mammalians and is involved in neuromodulatory functions. Since endocannabinoids were shown to be elevated in cerebrospinal fluid of epileptic dogs, knowledge about the species specific CB receptor expression in the nervous system is required. Therefore, we assessed the spatial distribution of CB1 receptors in the normal canine CNS and PNS...
2017: PloS One
https://www.readbyqxmd.com/read/28698140/n-arachidonoyl-glycine-another-endogenous-agonist-of-gpr55
#8
Linda Console-Bram, Sandra M Ciuciu, Pingwei Zhao, Robert E Zipkin, Eugen Brailoiu, Mary E Abood
Interest in lipoamino acids as endogenous modulators of G-protein coupled receptors has escalated due to their involvement in a variety of physiologic processes. In particular, a role for these amino acid conjugates has emerged in the endocannabinoid system. The study presented herein investigated the effects of N-arachidonoyl glycine (NAGly) on a candidate endocannabinoid receptor, GPR55. Our novel findings reveal that NAGly induces concentration dependent increases in calcium mobilization and mitogen-activated protein kinase activities in HAGPR55/CHO cells...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28695708/targeting-fatty-acid-amide-hydrolase-and-transient-receptor-potential-vanilloid-1-simultaneously-to-modulate-colonic-motility-and-visceral-sensation-in-the-mouse-a-pharmacological-intervention-with-n-arachidonoyl-serotonin-aa-5-ht
#9
M Bashashati, J Fichna, F Piscitelli, R Capasso, A A Izzo, A Sibaev, J-P Timmermans, N Cenac, N Vergnolle, V Di Marzo, M Storr
BACKGROUND: Endocannabinoid anandamide (AEA) inhibits intestinal motility and visceral pain, but it may also be proalgesic through transient receptor potential vanilloid-1 (TRPV1). AEA is degraded by fatty acid amide hydrolase (FAAH). This study explored whether dual inhibition of FAAH and TRPV1 reduces diarrhea and abdominal pain. METHODS: Immunostaining was performed on myenteric plexus of the mouse colon. The effects of the dual FAAH/TRPV1 inhibitor AA-5-HT on electrically induced contractility, excitatory junction potential (EJP) and fast (f) and slow (s) inhibitory junction potentials (IJP) in the mouse colon, colonic propulsion and visceromotor response (VMR) to rectal distension were studied...
July 11, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28694184/engineering-yeasts-as-platform-organisms-for-cannabinoid-biosynthesis
#10
Bastian Zirpel, Friederike Degenhardt, Chantale Martin, Oliver Kayser, Felix Stehle
Δ(9)-tetrahydrocannabinolic acid (THCA) is a plant derived secondary natural product from the plant Cannabis sativa l. The discovery of the human endocannabinoid system in the late 1980s resulted in a growing number of known physiological functions of both synthetic and plant derived cannabinoids. Thus, manifold therapeutic indications of cannabinoids currently comprise a significant area of research. Here we reconstituted the final biosynthetic cannabinoid pathway in yeasts. The use of the soluble prenyltransferase NphB from Streptomyces sp...
July 7, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28689299/4-o-methylhonokiol-protects-from-alcohol-carbon-tetrachloride-induced-liver-injury-in-mice
#11
Eleonora Patsenker, Andrea Chicca, Vanessa Petrucci, Sheida Moghadamrad, Andrea de Gottardi, Jochen Hampe, Jürg Gertsch, Nasser Semmo, Felix Stickel
Alcoholic liver disease (ALD) is a leading cause of liver cirrhosis, liver cancer, and related mortality. The endocannabinoid system contributes to the development of chronic liver diseases, where cannabinoid receptor 2 (CB2) has been shown to have a protecting role. Thus, here, we investigated how CB2 agonism by 4'-O-methylhonokiol (MHK), a biphenyl from Magnolia grandiflora, affects chronic alcohol-induced liver fibrosis and damage in mice. A combination of alcohol (10% vol/vol) and CCl4 (1 ml/kg) was applied to C57BL/6 mice for 5 weeks...
July 8, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28687674/anti-inflammatory-%C3%AF-3-endocannabinoid-epoxides
#12
Daniel R McDougle, Josephine E Watson, Amr A Abdeen, Reheman Adili, Megan P Caputo, John E Krapf, Rodney W Johnson, Kristopher A Kilian, Michael Holinstat, Aditi Das
Clinical studies suggest that diets rich in ω-3 polyunsaturated fatty acids (PUFAs) provide beneficial anti-inflammatory effects, in part through their conversion to bioactive metabolites. Here we report on the endogenous production of a previously unknown class of ω-3 PUFA-derived lipid metabolites that originate from the crosstalk between endocannabinoid and cytochrome P450 (CYP) epoxygenase metabolic pathways. The ω-3 endocannabinoid epoxides are derived from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to form epoxyeicosatetraenoic acid-ethanolamide (EEQ-EA) and epoxydocosapentaenoic acid-ethanolamide (EDP-EA), respectively...
July 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28686542/polyunsaturated-fatty-acids-and-endocannabinoids-in-health-and-disease
#13
Hércules Rezende Freitas, Alinny Rosendo Isaac, Renato Malcher-Lopes, Bruno Lourenço Diaz, Isis Hara Trevenzoli, Ricardo Augusto De Melo Reis
Polyunsaturated fatty acids (PUFAs) are lipid derivatives of omega-3 (docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA) or of omega-6 (arachidonic acid, ARA) synthesized from membrane phospholipids and used as a precursor for endocannabinoids (ECs). They mediate significant effects in the fine-tune adjustment of body homeostasis. Phyto- and synthetic cannabinoids also rule the daily life of billions worldwide, as they are involved in obesity, depression and drug addiction. Consequently, there is growing interest to reveal novel active compounds in this field...
July 7, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28685756/the-role-of-the-endocannabinoid-system-and-genetic-variation-in-adolescent-brain-development
#14
Heidi C Meyer, Francis S Lee, Dylan G Gee
During adolescence, both rodent and human studies have revealed dynamic changes in the developmental trajectories of corticolimbic structures, which are known to contribute to the regulation of fear and anxiety-related behaviors. The endocannabinoid (eCB) system critically regulates stress responsivity and anxiety throughout the lifespan. Emerging evidence suggests that during adolescence, changes in eCB signaling contribute to the maturation of local and corticolimbic circuit populations of neurons, such as mediating the balance between excitatory and inhibitory neurotransmission within the prefrontal cortex...
July 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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
#15
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/28685027/interactions-between-gut-microbes-and-host-cells-control-gut-barrier-and-metabolism
#16
REVIEW
P D Cani
Gut microbes are now considered as key partners involved in human physiology. Data have shown that microbes contribute to regulate energy, lipid, and glucose homeostasis through several mechanisms. Among them, the role of pathogen-associated molecular pattern and bacterial metabolites has been proposed (for example, metabolic endotoxemia and bioactive lipids). This short review, briefly discusses the role of the gut barrier as well as the impact of both the innate immune system and bioactive molecules (for example, endocannabinoids, cytochrome P450 derived arachidonic acids compounds) in the framework of gut microbes and cardiometabolic disorders...
December 2016: International Journal of Obesity Supplements
https://www.readbyqxmd.com/read/28680405/cannabinoids-and-vanilloids-in-schizophrenia-neurophysiological-evidence-and-directions-for-basic-research
#17
REVIEW
Rafael N Ruggiero, Matheus T Rossignoli, Jana B De Ross, Jaime E C Hallak, Joao P Leite, Lezio S Bueno-Junior
Much of our knowledge of the endocannabinoid system in schizophrenia comes from behavioral measures in rodents, like prepulse inhibition of the acoustic startle and open-field locomotion, which are commonly used along with neurochemical approaches or drug challenge designs. Such methods continue to map fundamental mechanisms of sensorimotor gating, hyperlocomotion, social interaction, and underlying monoaminergic, glutamatergic, and GABAergic disturbances. These strategies will require, however, a greater use of neurophysiological tools to better inform clinical research...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28680401/cannabidiol-is-a-potential-therapeutic-for-the-affective-motivational-dimension-of-incision-pain-in-rats
#18
Karina Genaro, Débora Fabris, Ana L F Arantes, Antônio W Zuardi, José A S Crippa, Wiliam A Prado
Background: Pain involves different brain regions and is critically determined by emotional processing. Among other areas, the rostral anterior cingulate cortex (rACC) is implicated in the processing of affective pain. Drugs that interfere with the endocannabinoid system are alternatives for the management of clinical pain. Cannabidiol (CBD), a phytocannabinoid found in Cannabis sativa, has been utilized in preclinical and clinical studies for the treatment of pain. Herein, we evaluate the effects of CBD, injected either systemically or locally into the rACC, on mechanical allodynia in a postoperative pain model and on the negative reinforcement produced by relief of spontaneous incision pain...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28677901/big-conductance-calcium-activated-potassium-channel-openers-control-spasticity-without-sedation
#19
David Baker, Gareth Pryce, Cristina Visintin, Sofia Sisay, Alexander I Bondarenko, W S Vanessa Ho, Samuel J Jackson, Thomas E Williams, Sarah Al-Izki, Ioanna Sevastou, Masahiro Okuyama, Wolfgang F Graier, Lesley A Stevenson, Carolyn Tanner, Ruth Ross, Roger G Pertwee, Christopher M Henstridge, Andrew J Irving, Jesse Schulman, Keith Powell, Mark D Baker, Gavin Giovannoni, David L Selwood
BACKGROUND & PURPOSE: The initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis, whilst avoiding the sedative, side-effect-potential associated with cannabis. (R,Z)-3-(6-(dimethylamino)-6-oxohex-1-enyl)-N-(1-hydroxypropan-2-yl)benzamide (VSN16R) was synthesized as an anandamide (endocannabinoid) analogue in an anti-metabolite approach to identify drug-like agents to target spasticity. EXPERIMENTAL APPROACH: Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue-based assays and in vivo animal models, were used to demonstrate: activity, efficacy, pharmacokinetics and mechanism of action of the molecule...
July 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28675945/impact-of-dietary-fat-on-gut-microbiota-and-low-grade-systemic-inflammation-mechanisms-and-clinical-implications-on-obesity
#20
Flávia Galvão Cândido, Flávia Xavier Valente, Łukasz Marcin Grześkowiak, Ana Paula Boroni Moreira, Daniela Mayumi Usuda Prado Rocha, Rita de Cássia Gonçalves Alfenas
Dietary fat strongly affects human health by modulating gut microbiota composition and low-grade systemic inflammation. High-fat diets have been implicated in reduced gut microbiota richness, increased Firmicutes to Bacteroidetes ratio, and several changes at family, genus and species levels. Saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA) and conjugated linolenic fatty acids share important pathways of immune system activation/inhibition with gut microbes, modulating obesogenic and proinflammatory profiles...
July 4, 2017: International Journal of Food Sciences and Nutrition
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