title: Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide.
abstract: Cannabinoids have recently been approved as a treatment for pain in multiple sclerosis (MS). Increasing evidence from animal studies suggests that this class of compounds could also prove efficient to fight neurodegeneration, demyelination, inflammation and autoimmune processes occurring in this pathology. However, the use of cannabinoids is limited by their psychoactive effects. In this context, potentiation of the endogenous cannabinoid signalling could represent a substitute to the use of exogenously administrated cannabinoid ligands. Here, we studied the expression of different elements of the endocannabinoid system in a chronic model of MS in mice. We first studied the expression of the two cannabinoid receptors, CB(1) and CB(2), as well as the putative intracellular cannabinoid receptor peroxisome proliferator-activated receptor-alpha. We observed an upregulation of CB(2), correlated to the production of proinflammatory cytokines, at 60 days after the onset of the MS model. At this time, the levels of the endocannabinoid, 2-arachidonoylglycerol, and of the anti-inflammatory anandamide congener, palmithoylethanolamide, were enhanced, without changes in the levels of anandamide. These changes were not due to differences in the expression of the degradation enzymes, fatty acid amide hydrolase and monoacylglycerol lipase, or of biosynthetic enzymes, diacylglycerol lipase-alpha and N-acylphosphatidylethanolamine phospholipase-D at this time (60 days). Finally, the exogenous administration of palmitoylethanolamide resulted in a reduction of motor disability in the animals subjected to this model of MS, accompanied by an anti-inflammatory effect. This study overall highlights the potential therapeutic effects of endocannabinoids in MS.
authors.affiliation: Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Frida
authors.initials: F
authors.lastname: Loría
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Leyre
authors.initials: L
authors.lastname: Mestre
authors.forename: Alessandra
authors.initials: A
authors.lastname: Spagnolo
authors.forename: Fernando
authors.initials: F
authors.lastname: Correa
authors.forename: Miriam
authors.initials: M
authors.lastname: Hernangómez
authors.forename: Carmen
authors.initials: C
authors.lastname: Guaza
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Fabian
authors.initials: F
authors.lastname: Docagne
mesh_terms: D000577:Amides; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D063388:Endocannabinoids; D004983:Ethanolamines; D005260:Female; D006801:Humans; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D010146:Pain / Q000188:drug therapy; D010169:Palmitic Acids / Q000378:metabolism / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism; D045442:Rotarod Performance Test; D015398:Signal Transduction / Q000502:physiology*; D017945:Theilovirus / Q000276:immunology
chemical_list: D000577:Amides; D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D063385:Cannabinoid Receptor Modulators; D016207:Cytokines; D063388:Endocannabinoids; D004983:Ethanolamines; D047493:PPAR alpha; D010169:Palmitic Acids; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C005958:palmidrol