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https://www.readbyqxmd.com/read/28213089/monoglyceride-lipase-as-a-drug-target-at-the-crossroads-of-arachidonic-acid-metabolism-and-endocannabinoid-signaling
#1
REVIEW
Gernot F Grabner, Robert Zimmermann, Rudolf Schicho, Ulrike Taschler
Monoglyerides (MGs) are short-lived, intermediary lipids deriving from the degradation of phospho- and neutral lipids, and monoglyceride lipase (MGL), also designated as monoacylglycerol lipase (MAGL), is the major enzyme catalyzing the hydrolysis of MGs into glycerol and fatty acids. This distinct function enables MGL to regulate a number of physiological and pathophysiological processes since both MGs and fatty acids can act as signaling lipids or precursors thereof. The most prominent MG species acting as signaling lipid is 2-arachidonoylglycerol (2-AG) which is the most abundant endogenous agonist of cannabinoid receptors in the body...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28210207/cannabinoid-receptor-2-signaling-in-neurodegenerative-disorders-from-pathogenesis-to-a-promising-therapeutic-target
#2
REVIEW
Tommaso Cassano, Silvio Calcagnini, Lorenzo Pace, Federico De Marco, Adele Romano, Silvana Gaetani
As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically. Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28209996/transient-cannabinoid-receptor-2-blockade-during-immunization-heightens-intensity-and-breadth-of-antigen-specific-antibody-responses-in-young-and-aged-mice
#3
Emmanuel Dotsey, Irina Ushach, Egest Pone, Rie Nakajima, Algis Jasinskas, Donovan A Argueta, Andrea Dillon, Nicholas DiPatrizio, Huw Davies, Albert Zlotnik, Peter D Crompton, Philip L Felgner
The hallmark of vaccines is their ability to prevent the spread of infectious pathogens and thereby serve as invaluable public health tool. Despite their medical relevance, there is a gap in our understanding of the physiological factors that mediate innate and adaptive immune response to vaccines. The endocannabinoid (eCB) system is a critical modulator of homeostasis in vertebrates. Our results indicate that macrophages and dendritic cells produce the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG) upon antigen activation...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209735/the-epac-phospholipase-c%C3%AE%C2%B5-pathway-regulates-endocannabinoid-signaling-and-cocaine-induced-disinhibition-of-vta-dopamine-neurons
#4
Jiaqing Tong, Xiaojie Liu, Casey Vickstrom, Yan Li, Laikang Yu, Youming Lu, Alan V Smrcka, Qing-Song Liu
Exchange protein directly activated by cAMP (Epac) is a direct effector for the ubiquitous second messenger cAMP. Epac activates the phospholipase Cε (PLCε) pathway. PLCβ has been linked to the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Here, we report that Epac facilitates endocannabinoid-mediated retrograde synaptic depression through activation of PLCε. Intracellular loading of a selective Epac agonist 8-CPT-2Me-cAMP into ventral tegmental area (VTA) dopamine neurons enabled previously ineffective stimuli to induce depolarization-induced suppression of inhibition (DSI) and long-term depression of IPSCs (I-LTD) in the VTA...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28201982/transcriptome-profile-of-rat-genes-in-injured-spinal-cord-at-different-stages-by-rna-sequencing
#5
Ling-Ling Shi, Nan Zhang, Xiu-Mei Xie, Yue-Juan Chen, Rui Wang, Lin Shen, Jian-Sheng Zhou, Jian-Guo Hu, He-Zuo Lü
BACKGROUND: Spinal cord injury (SCI) results in fatal damage and currently has no effective treatment. The pathological mechanisms of SCI remain unclear. In this study, genome-wide transcriptional profiling of spinal cord samples from injured rats at different time points after SCI was performed by RNA-Sequencing (RNA-Seq). The transcriptomes were systematically characterized to identify the critical genes and pathways that are involved in SCI pathology. RESULTS: RNA-Seq results were obtained from total RNA harvested from the spinal cords of sham control rats and rats in the acute, subacute, and chronic phases of SCI (1 day, 6 days and 28 days after injury, respectively; n = 3 in every group)...
February 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28193523/faah-inhibition-produces-antidepressant-like-efforts-of-mice-to-acute-stress-via-synaptic-long-term-depression
#6
Ying Wang, Xia Zhang
Recent studies have shown that inhibition of fatty acid amide hydrolase (FAAH), the major degradative enzyme of the endocannabinoid N-arachidonoylethanolamine (AEA), produced antidepressant behavioral responses, but its underlying mechanism is not clear. Here we find that a systemic administration of the FAAH inhibitor PF3845 or an intra-CA1 application of AEA elicits an in vivo long-term depression (LTD) at excitatory glutamatergic CA3-CA1 synapses of the hippocampus. The PF3845- and/or AEA-elicited LTD are abolished by the LTD-blocking peptide Tat-GluR2...
February 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28193521/pharmacological-inhibition-of-magl-lipase-attenuates-experimental-colon-carcinogenesis
#7
Ester Pagano, Francesca Borrelli, Pierangelo Orlando, Barbara Romano, Martina Monti, Lucia Morbidelli, Gabriella Aviello, Roberta Imperatore, Raffaele Capasso, Fabiana Piscitelli, Lorena Buono, Vincenzo Di Marzo, Angelo A Izzo
Colorectal cancer (CRC) is a major health problem in Western countries. The endocannabinoid 2-arachidonoyl-glycerol (2-AG) exerts antiproliferative actions in a number of tumoral cell lines, including CRC cells. Monoacylglycerol lipase (MAGL), a serine hydrolase that inactivates 2-AG, is highly expressed in aggressive human cancer cells. Here, we investigated the role of MAGL in experimental colon carcinogenesis. The role of MAGL was assessed in vivo by using the xenograft and the azoxymethane models of colon carcinogenesis; MAGL expression was evaluated by RT-PCR and immunohistochemistry; 2-AG levels were measured by liquid chromatography mass spectrometry; angiogenesis was evaluated in tumor tissues [by microvessel counting and by investigating the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) proteins] as well as in human umbilical vein endothelial cells (HUVEC); cyclin D1 was evaluated by RT-PCR...
February 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28192193/differential-expression-of-endocannabinoid-system-related-genes-in-the-dorsal-hippocampus-following-expression-and-reinstatement-of-morphine-conditioned-place-preference-in-mice
#8
Wei Li, Cong-Li Zhang, Zheng-Guo Qiu
The endocannabinoid signaling plays a critical role in mediating rewarding effects to morphine. The relative stability for the expression and reinstatement of morphine conditioned place preference (CPP) suggests the involvement of differential neuroadaptations in learned associations between environmental cues and morphine. Changes in gene expression in hippocampus through the endogenous cannabinoid system (eCB) may accompany and mediate the development of such neuroadaptations to repeated morphine stimulation...
February 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28192082/endocannabinoid-dependent-protection-against-kainic-acid-induced-long-term-alteration-of-brain-oscillations-in-guinea-pigs
#9
Liubov Shubina, Rubin Aliev, Valentina Kitchigina
Changes in rhythmic activity can serve as early biomarkers of pathological alterations, but it remains unclear how different types of rhythmic activity are altered during neurodegenerative processes. Glutamatergic neurotoxicity, evoked by kainic acid (KA), causes hyperexcitation and acute seizures that result in delayed brain damage. We employed wide frequency range (0.1-300 Hz) local field potential recordings in guinea pigs to study the oscillatory activity of the hippocampus, entorhinal cortex, medial septum, and amygdala in healthy animals for three months after KA introduction...
February 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28191598/diacylglycerol-kinase-%C3%AE%C2%B5-localizes-to-subsurface-cisterns-of-cerebellar-purkinje-cells
#10
Yasukazu Hozumi, Hiroki Fujiwara, Kenya Kaneko, Satoshi Fujii, Matthew K Topham, Masahiko Watanabe, Kaoru Goto
Following activation of Gq protein-coupled receptors, phospholipase C yields a pair of second messengers: diacylglycerol (DG) and inositol 1,4,5-trisphosphate. Diacylglycerol kinase (DGK) phosphorylates DG to produce phosphatidic acid, another second messenger. Of the DGK family, DGKε is the only DGK isoform that exhibits substrate specificity for DG with an arachidonoyl acyl chain at the sn-2 position. Recently, we demonstrated that hydrophobic residues in the N-terminus of DGKε play an important role in targeting the endoplasmic reticulum in transfected cells...
February 13, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28190698/therapeutic-effects-of-cannabinoids-in-animal-models-of-seizures-epilepsy-epileptogenesis-and-epilepsy-related-neuroprotection
#11
REVIEW
Evan C Rosenberg, Pabitra H Patra, Benjamin J Whalley
The isolation and identification of the discrete plant cannabinoids in marijuana revived interest in analyzing historical therapeutic claims made for cannabis in clinical case studies and anecdotes. In particular, sources as old as the 11th and 15th centuries claimed efficacy for crude marijuana extracts in the treatment of convulsive disorders, prompting a particularly active area of preclinical research into the therapeutic potential of plant cannabinoids in epilepsy. Since that time, a large body of literature has accumulated describing the effects of several of the >100 individual plant cannabinoids in preclinical models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection...
February 9, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28182408/design-synthesis-structure-activity-relationship-studies-and-three-dimensional-quantitative-structure-activity-relationship-3d-qsar-modeling-of-a-series-of-o-biphenyl-carbamates-as-dual-modulators-of-dopamine-d3-receptor-and-fatty-acid-amide-hydrolase
#12
Alessio De Simone, Debora Russo, Gian Filippo Ruda, Alessandra Micoli, Mariarosaria Ferraro, Rita Maria Concetta Di Martino, Giuliana Ottonello, Maria Summa, Andrea Armirotti, Tiziano Bandiera, Andrea Cavalli, Giovanni Bottegoni
We recently reported molecules designed according to the multi-target-directed ligand paradigm to exert combined activity at human fatty acid amide hydrolase (FAAH) and dopamine receptor subtype D3 (D3R). Both targets are relevant for tackling several types of addiction (most notably nicotine addiction) and other compulsive behaviors. Here, we report an SAR exploration of a series of biphenyl-N-[4-[4-(2,3-substituted-phenyl)piperazine-1-yl]alkyl]carbamates, a novel class of molecules that had shown promising activities at the FAAH - D3R target combination in preliminary studies...
February 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28173961/a-screen-for-modulators-reveals-that-orexin-a-rapidly-stimulates-thyrotropin-releasing-hormone-expression-and-release-in-hypothalamic-cell-culture
#13
Antonieta Cote-Vélez, Anabel Martínez Báez, Leticia Lezama, Rosa María Uribe, Patricia Joseph-Bravo, Jean-Louis Charli
In the paraventricular nucleus of the mammalian hypothalamus, hypophysiotropic thyrotropin releasing hormone (TRH) neurons integrate metabolic information and control the activity of the thyroid axis. Additional populations of TRH neurons reside in various hypothalamic areas, with poorly defined connections and functions, albeit there is evidence that some may be related to energy balance. To establish extracellular modulators of TRH hypothalamic neurons activity, we performed a screen of neurotransmitters effects in hypothalamic cultures...
February 2, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28168010/rutin-as-a-mediator-of-lipid-metabolism-and-cellular-signaling-pathways-interactions-in-fibroblasts-altered-by-uva-and-uvb-radiation
#14
Agnieszka Gęgotek, Paula Rybałtowska-Kawałko, Elżbieta Skrzydlewska
Background. Rutin is a natural nutraceutical that is a promising compound for the prevention of UV-induced metabolic changes in skin cells. The aim of this study was to examine the effects of rutin on redox and endocannabinoid systems, as well as proinflammatory and proapoptotic processes, in UV-irradiated fibroblasts. Methods. Fibroblasts exposed to UVA and UVB radiation were treated with rutin. The activities and levels of oxidants/antioxidants and endocannabinoid system components, as well as lipid, DNA, and protein oxidation products, and the proinflammatory and pro/antiapoptotic proteins expression were measured...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28166699/planhab-study-assessment-of-psycho-neuroendocrine-function-in-male-subjects-during-21-days-of-normobaric-hypoxia-and-bed-rest
#15
C Strewe, R Zeller, M Feuerecker, M Hoerl, I Kumprej, A Crispin, B Johannes, T Debevec, I Mekjavic, G Schelling, A Choukèr
Immobilization and hypoxemia are conditions often seen in patients suffering from severe heart insufficiency or primary pulmonary diseases (e.g. fibrosis, emphysema). In future planned long-duration and exploration class space missions (including habitats on the moon and Mars), healthy individuals will encounter such a combination of reduced physical activity and oxygen tension by way of technical reasons and the reduced gravitational forces. These overall unconventional extraterrestrial conditions can result in yet unknown consequences for the regulation of stress-permissive, psycho-neuroendocrine responses, which warrant appropriate measures in order to mitigate foreseeable risks...
February 6, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/28164368/bdnf-induced-endocannabinoid-release-modulates-neocortical-glutamatergic-neurotransmission
#16
Mason L Yeh, Rajamani Selvam, Eric S Levine
Endocannabinoids (eCBs) and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), are potent neuromodulators found throughout the mammalian neocortex. Both eCBs and BDNF play critical roles in many behavioral and neurophysiological processes and are targets for the development of novel therapeutics. The effects of eCBs and BDNF are primarily mediated by the type 1 cannabinoid (CB1) receptor and the trkB tyrosine kinase receptor, respectively. Our laboratory and others have previously established that BDNF potentiates excitatory transmission by enhancing presynaptic glutamate release and modulating NMDA receptors...
February 6, 2017: Synapse
https://www.readbyqxmd.com/read/28164346/randomised-clinical-trial-the-analgesic-properties-of-dietary-supplementation-with-palmitoylethanolamide-and-polydatin-in-irritable-bowel-syndrome
#17
C Cremon, V Stanghellini, M R Barbaro, R F Cogliandro, L Bellacosa, J Santos, M Vicario, M Pigrau, C Alonso Cotoner, B Lobo, F Azpiroz, S Bruley des Varannes, M Neunlist, D DeFilippis, T Iuvone, S Petrosino, V Di Marzo, G Barbara
BACKGROUND: Intestinal immune activation is involved in irritable bowel syndrome (IBS) pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation. Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation. AIM: To assess the effect on mast cell count and the efficacy of palmithoylethanolamide/polydatin in patients with IBS...
February 6, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28162376/-152-the-endocannabinoid-system-current-knowledge-and-future-directions
#18
D Gray
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28161834/cannabinoid-receptors-in-regulating-the-gi-tract-experimental-evidence-and-therapeutic-relevance
#19
Ulrike Taschler, Carina Hasenoehrl, Martin Storr, Rudolf Schicho
Cannabinoid receptors are fundamentally involved in all aspects of intestinal physiology, such as motility, secretion, and epithelial barrier function. They are part of a broader entity, the so-called endocannabinoid system which also includes their endocannabinoid ligands and the ligands' synthesizing/degrading enzymes. The system has a strong impact on the pathophysiology of the gastrointestinal tract and is believed to maintain homeostasis in the gut by controlling hypercontractility and by promoting regeneration after injury...
February 5, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28161439/lipid-signaling-and-fat-storage-in-the-dark-eyed-junco
#20
Jacqueline M Ho, Christine M Bergeon Burns, Nikki M Rendon, Kimberly A Rosvall, Heather B Bradshaw, Ellen D Ketterson, Gregory E Demas
Seasonal hyperphagia and fattening promote survivorship in migratory and wintering birds, but reduced adiposity may be more advantageous during the breeding season. Factors such as photoperiod, temperature, and food predictability are known environmental determinants of fat storage, but the underlying neuroendocrine mechanisms are less clear. Endocannabinoids and other lipid signaling molecules regulate multiple aspects of energy balance including appetite and lipid metabolism. However, these functions have been established primarily in mammals; thus the role of lipid signals in avian fat storage remains largely undefined...
February 1, 2017: General and Comparative Endocrinology
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