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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.
Eur J Neurosci. 2008 Aug; 28(4):633-41.EJ

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+Show Affiliations

Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18657182

Citation

Loría, Frida, et al. "Study of the Regulation of the Endocannabinoid System in a Virus Model of Multiple Sclerosis Reveals a Therapeutic Effect of Palmitoylethanolamide." The European Journal of Neuroscience, vol. 28, no. 4, 2008, pp. 633-41.
Loría F, Petrosino S, Mestre L, et al. Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide. Eur J Neurosci. 2008;28(4):633-41.
Loría, F., Petrosino, S., Mestre, L., Spagnolo, A., Correa, F., Hernangómez, M., Guaza, C., Di Marzo, V., & Docagne, F. (2008). Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide. The European Journal of Neuroscience, 28(4), 633-41. https://doi.org/10.1111/j.1460-9568.2008.06377.x
Loría F, et al. Study of the Regulation of the Endocannabinoid System in a Virus Model of Multiple Sclerosis Reveals a Therapeutic Effect of Palmitoylethanolamide. Eur J Neurosci. 2008;28(4):633-41. PubMed PMID: 18657182.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide. AU - Loría,Frida, AU - Petrosino,Stefania, AU - Mestre,Leyre, AU - Spagnolo,Alessandra, AU - Correa,Fernando, AU - Hernangómez,Miriam, AU - Guaza,Carmen, AU - Di Marzo,Vincenzo, AU - Docagne,Fabian, Y1 - 2008/07/24/ PY - 2008/7/29/pubmed PY - 2008/10/22/medline PY - 2008/7/29/entrez SP - 633 EP - 41 JF - The European journal of neuroscience JO - Eur. J. Neurosci. VL - 28 IS - 4 N2 - 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. SN - 1460-9568 UR - https://www.unboundmedicine.com/medline/citation/18657182/Study_of_the_regulation_of_the_endocannabinoid_system_in_a_virus_model_of_multiple_sclerosis_reveals_a_therapeutic_effect_of_palmitoylethanolamide_ L2 - https://doi.org/10.1111/j.1460-9568.2008.06377.x DB - PRIME DP - Unbound Medicine ER -