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Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide
Author(s) -
Loría Frida,
Petrosino Stefania,
Mestre Leyre,
Spagnolo Alessandra,
Correa Fernando,
Hernangómez Miriam,
Guaza Carmen,
Di Marzo Vincenzo,
Docagne Fabian
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06377.x
Subject(s) - palmitoylethanolamide , endocannabinoid system , anandamide , monoacylglycerol lipase , 2 arachidonoylglycerol , cannabinoid receptor , fatty acid amide hydrolase , diacylglycerol lipase , cannabinoid , proinflammatory cytokine , pharmacology , depolarization induced suppression of inhibition , chemistry , cannabinoid receptor type 2 , receptor , biology , inflammation , agonist , medicine , biochemistry
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‐α. 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‐α 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.