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Nóra Zákány, Attila Oláh, Arnold Markovics, Erika Takács, Andrea Aranyász, Simon Nicolussi, Fabiana Piscitelli, Marco Allarà, Ágnes Pór, Ilona Kovács, Christos C Zouboulis, Jürg Gertsch, Vincenzo Di Marzo, Tamás Bíró, Tamás Szabó
We have previously shown that i) endocannabinoids (eCB; e.g. anandamide [AEA]) are involved in the maintenance of homeostatic sebaceous lipid production (SLP) in human sebaceous glands (SG); and ii) eCB treatment dramatically increases SLP. Here, we aimed to investigate the expression of the major eCB synthesizing and degrading enzymes, and to study the effects of eCB uptake inhibitors on human SZ95 sebocytes, thus exploring the role of the putative eCB membrane transporter (EMT), which has been hypothesized to facilitate the cellular uptake and subsequent degradation of eCBs...
February 28, 2018: Journal of Investigative Dermatology
Rose Chesworth, Leonora E Long, Cynthia Shannon Weickert, Tim Karl
The use of cannabis is a well-established component risk factor for schizophrenia, particularly in adolescent individuals with genetic predisposition for the disorder. Alterations to the endocannabinoid system have been found in the prefrontal cortex of patients with schizophrenia. Thus, we assessed whether molecular alterations exist in the endocannabinoid signalling pathway during brain development in a mouse model for the schizophrenia risk gene neuregulin 1 ( Nrg1 ). We analysed transcripts encoding key molecules of the endocannabinoid system in heterozygous transmembrane domain Nrg1 mutant mice ( Nrg1 TM HET), which is known to have increased sensitivity to cannabis exposure...
2018: Frontiers in Psychiatry
Kushal Gandhi, Cun Li, Nadezhda German, Cezary Skobowiat, Maira Carrillo, Raja Reddy Kallem, Eneko Larumbe, Stacy Martinez, Marcel Chuecos, Gary Ventolini, Peter Nathanielsz, Natalia Schlabritz-Loutsevitch
INTRODUCTION: Involvement of endogenous cannabinoids (eCBs) in obesity is well-characterized. However, information regarding eCB physiology in obesity associated with pregnancy is sparse. METHODS: From at least 9 months before conception, non-pregnant baboons (Papio spp.) were fed a diet of either 45% fat (HFD; n=11) or 12% fat or a control diet (CTR; n=11), and dietary intervention continued through pregnancy. Maternal and fetal venous plasma samples were evaluated using liquid chromatography-mass spectrometry to quantify anandamide (AEA) and 2-arachidonoyl glycerol (2-AG)...
November 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
Felix Schreiner, Merle Ackermann, Michael Michalik, Eva Hucklenbruch-Rother, Andras Bilkei-Gorzo, Ildiko Racz, Laura Bindila, Beat Lutz, Jörg Dötsch, Andreas Zimmer, Joachim Woelfle
BACKGROUND: Nutrient deprivation during early development has been associated with the predisposition to metabolic disorders in adulthood. Considering its interaction with metabolism, appetite and behavior, the endocannabinoid (eCB) system represents a promising target of developmental programming. METHODS: By cross-fostering and variation of litter size, early postnatal nutrition of CB6F1-hybrid mice was controlled during the lactation period (3, 6, or 10 pups/mother)...
2017: PloS One
Mariana I Holubiec, Juan I Romero, Eduardo Blanco, Tamara Logica Tornatore, Juan Suarez, Fernando Rodríguez de Fonseca, Pablo Galeano, Francisco Capani
Endocannabinoids (eCBs) and acylethanolamides (AEs) have lately received more attention due to their neuroprotective functions in neurological disorders. Here we analyze the alterations induced by perinatal asphyxia (PA) in the main metabolic enzymes and receptors of the eCBs/AEs in the dorsal striatum of rats. To induce PA, we used a model developed by Bjelke et al. (1991). Immunohistochemical techniques were carried out to determine the expression of neuronal and glial markers (NeuN and GFAP), eCBs/AEs synthesis and degradation enzymes (DAGLα, NAPE-PLD and FAAH) and their receptors (CB1 and PPARα)...
July 13, 2017: Neuroscience Letters
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
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...
March 16, 2017: Neuroscience Letters
Allison H Hahn, Devin P Merullo, Jeremy A Spool, Caroline S Angyal, Sharon A Stevenson, Lauren V Riters
Vocal communication is required for successful social interactions in numerous species. During the breeding season, songbirds produce songs that are reinforced by behavioral consequences (e.g., copulation). However, some songbirds also produce songs not obviously directed at other individuals. The consequences maintaining or reinforcing these songs are less obvious and the neural mechanisms associated with undirected communication are not well-understood. Previous studies indicate that undirected singing is intrinsically rewarding and mediated by opioid or dopaminergic systems; however, endocannabinoids are also involved in regulating reward and singing behavior...
March 27, 2017: Neuroscience
Arsalan Jafarpour, Faramarz Dehghani, Horst-Werner Korf
Endocannabinoids (ECs) are ubiquitous endogenous lipid derivatives and play an important role in intercellular communication either in an autocrine/paracrine or in an endocrine fashion. Recently, an intrinsic EC system has been discovered in the hypophysial pars tuberalis (PT) of hamsters and humans. In hamsters, this EC system is under photoperiodic control and appears to influence the secretion of hormones such as prolactin from the adenohypophysis. We investigate the EC system in the PT of the rat, a frequently used species in endocrine research...
April 2017: Cell and Tissue Research
Andrea Martella, Rosa M Sepe, Cristoforo Silvestri, Jingjing Zang, Giulia Fasano, Oliana Carnevali, Paolo De Girolamo, Stephan C F Neuhauss, Paolo Sordino, Vincenzo Di Marzo
The developmental role of the endocannabinoid system still remains to be fully understood. Here, we report the presence of a complete endocannabinoid system during zebrafish development and show that the genes that code for enzymes that catalyze the anabolism and catabolism (mgll and dagla) of the endocannabinoid, 2-AG (2-arachidonoylglycerol), as well as 2-AG main receptor in the brain, cannabinoid receptor type 1, are coexpressed in defined regions of axonal growth. By using morpholino-induced transient knockdown of the zebrafish Daglα homolog and its pharmacologic rescue, we suggest that synthesis of 2-AG is implicated in the control of axon formation in the midbrain-hindbrain region and that animals that lack Daglα display abnormal physiological behaviors in tests that measure stereotyped movement and motion perception...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ya Zhou, Fiona V Howell, Oleg O Glebov, David Albrecht, Gareth Williams, Patrick Doherty
Diacylglycerol lipase alpha (DAGLα) generates the endocannabinoid (eCB) 2-arachidonylglycerol (2-AG) that regulates the proliferation and differentiation of neural stem cells and serves as a retrograde signaling lipid at synapses. Nothing is known about the dynamics of DAGLα expression in cells and this is important as it will govern where 2-AG can be made and released. We have developed a new construct to label DAGLα at the surface of live cells and follow its trafficking. In hippocampal neurons a cell surface pool of DAGLα co-localizes with Homer, a postsynaptic density marker...
October 2016: Molecular and Cellular Neurosciences
Angela M Henricks, Anthony L Berger, Janelle M Lugo, Lydia N Baxter-Potter, Kennedy V Bieniasz, Rebecca M Craft, Ryan J McLaughlin
Chronic intermittent alcohol (CIA) exposure produces altered motivational states characterized by anxiety and escalated alcohol consumption during withdrawal. The endocannabinoid (ECB) system contributes to these symptoms, and sex differences in alcohol dependence, as well as bidirectional interactions between ECBs and gonadal hormones have been documented. Thus, we evaluated sex differences in alcohol consumption, anxiety-like behavior, and ECB mRNA expression in the nucleus accumbens (NAc) of alcohol-dependent rats during acute withdrawal...
October 29, 2016: Neuroscience
Iram P Rodriguez-Sanchez, Josee Guindon, Marco Ruiz, M Elizabeth Tejero, Gene Hubbard, Laura E Martinez-de-Villarreal, Hugo A Barrera-Saldaña, Edward J Dick, Anthony G Comuzzie, Natalia E Schlabritz-Loutsevitch
INTRODUCTION: The consumption of marijuana (exogenous cannabinoid) almost doubled in adults during last decade. Consumption of exogenous cannabinoids interferes with the endogenous cannabinoid (or "endocannabinoid" (eCB)) system (ECS), which comprises N-arachidonylethanolamide (anandamide, AEA), 2-arachidonoyl glycerol (2-AG), endocannabinoid receptors (cannabinoid receptors 1 and 2 (CB1R and CB2R), encoded by CNR1 and CNR2, respectively), and synthesizing/degrading enzymes (FAAH, fatty-acid amide hydrolase; MAGL, monoacylglycerol lipase; DAGL-α, diacylglycerol lipase-alpha)...
November 2016: Neurotoxicology and Teratology
Tiziana Bisogno
The endocannabinoid 2-arachidonoylglycerol (2-AG) exerts its physiological action by binding to and functionally activating type-1 (CB1) and type-2 (CB2) cannabinoid receptors. It is thought to be produced through the action of sn-1 selective diacylglycerol lipase (DAGL) that catalyzes 2-AG biosynthesis from sn-2-arachidonate-containing diacylglycerols. Since 2-AG biosynthetic enzymes have been identified only recently, little information on methodological approaches for measuring DAGL activity is as yet available...
2016: Methods in Molecular Biology
Gregory G Martin, Sarah Chung, Danilo Landrock, Kerstin K Landrock, Huan Huang, Lawrence J Dangott, Xiaoxue Peng, Martin Kaczocha, Drew R Seeger, Eric J Murphy, Mikhail Y Golovko, Ann B Kier, Friedhelm Schroeder
Liver fatty acid-binding protein (FABP1, L-FABP) has high affinity for and enhances uptake of arachidonic acid (ARA, C20:4, n-6) which, when esterified to phospholipids, is the requisite precursor for synthesis of endocannabinoids (EC) such as arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). The brain derives most of its ARA from plasma, taking up ARA and transporting it intracellularly via cytosolic fatty acid-binding proteins (FABPs 3,5, and 7) localized within the brain. In contrast, the much more prevalent cytosolic FABP1 is not detectable in the brain but is instead highly expressed in the liver...
August 2016: Journal of Neurochemistry
Lindsey A Knake, Monika Ahuja, Erin L McDonald, Kelli K Ryckman, Nancy Weathers, Todd Burstain, John M Dagle, Jeffrey C Murray, Prakash Nadkarni
BACKGROUND: The use of Electronic Health Records (EHR) has increased significantly in the past 15 years. This study compares electronic vs. manual data abstractions from an EHR for accuracy. While the dataset is limited to preterm birth data, our work is generally applicable. We enumerate challenges to reliable extraction, and state guidelines to maximize reliability. METHODS: An Epic™ EHR data extraction of structured data values from 1,772 neonatal records born between the years 2001-2011 was performed...
April 29, 2016: BMC Pediatrics
Praveen K Singh, Rachel Markwick, Leanne Lu, Fiona V Howell, Gareth Williams, Patrick Doherty
The diacylglycerol lipases (DAGLα and DAGLβ) hydrolyze DAG to generate 2-arachidonoylglycerol (2-AG), the principal endocannabinoid and main precursor of arachidonic acid (AA). The DAGLs make distinct tissue specific contributions toward 2-AG and AA levels, and therefore, selective modulators for these enzymes could play crucial roles toward harnessing their therapeutic potential. Relatively high-throughput assays have recently been reported for DAGLα and have proven useful toward the characterization of inhibitors of this enzyme...
May 17, 2016: Biochemistry
Alonso Vilches-Flores, Zara Franklin, Astrid C Hauge-Evans, Bo Liu, Guo C Huang, Pratik Choudhary, Peter M Jones, Shanta J Persaud
BACKGROUND: Although in vivo studies have implicated endocannabinoids in metabolic dysfunction, little is known about direct, chronic activation of the endocannabinoid system (ECS) in human islets. Therefore, this study investigated the effects of prolonged exposure to cannabinoid agonists on human islet gene expression and function. METHODS: Human islets were maintained for 2 and 5 days in the absence or presence of CB1r (ACEA) or CB2r (JWH015) agonists. Gene expression was quantified by RT-PCR, hormone levels by radioimmunoassay and apoptosis by caspase activities...
June 2016: BBA Clinical
Anne L Smazal, Anne B Kavars, Susan J Carlson, Tarah T Colaizy, John M Dagle
BACKGROUND: While very preterm (<32 wk gestation) infants are routinely provided intensive nutritional support via central line, clinical practice varies for nutrient delivery in infants born moderately preterm (32-34 wk gestation). We sought to define the impact of nutritional support via peripherally inserted central catheter (PICC) on nutrient delivery in the first 2 wk of life and growth by discharge. METHODS: Data were extracted from the records of 187 infants born between 32 and 34 6/7 wk gestation and admitted to the University of Iowa Children's Hospital between April 2012 and December 2013...
August 2016: Pediatric Research
Praveen K Singh, Rachel Markwick, Fiona V Howell, Gareth Williams, Patrick Doherty
Diacylglycerol lipase α (DAGLα) hydrolyses DAG to generate the principal endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) in the central nervous system. DAGLα dependent cannabinoid (CB) signalling has been implicated in numerous processes including axonal growth and guidance, adult neurogenesis and retrograde signalling at the synapse. Recent studies have implicated DAGLα as an emerging drug target for several conditions including pain and obesity. Activity assays are critical to the drug discovery process; however, measurement of diacylglycerol lipase (DAGL) activity using its native substrate generally involves low-throughput MS techniques...
June 2016: Bioscience Reports
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