Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide

Authors

  • Frida Loría,

    1. Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain
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  • Stefania Petrosino,

    1. Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Napoli, Italy
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  • Leyre Mestre,

    1. Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain
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  • Alessandra Spagnolo,

    1. Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain
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  • Fernando Correa,

    1. Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain
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  • Miriam Hernangómez,

    1. Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain
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  • Carmen Guaza,

    1. Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain
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  • Vincenzo Di Marzo,

    1. Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Napoli, Italy
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  • Fabian Docagne

    1. Neuroimmunology Group, Department of Functional and Systems Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain
    2. INSERM, INSERM U919 ‘serine proteases and pathophysiology of the neurovascular unit’, GIP Cyceron, Caen Cedex, France
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    • *

      Present address: INSERM U919, SP2U, GIP Cyceron, Bd H. Becquerel, BP 5229, 14074 Caen Cedex, France.


Dr F. Docagne, at *present address below.
E-mail: docagne@cyceron.fr

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, CB1 and CB2, as well as the putative intracellular cannabinoid receptor peroxisome proliferator-activated receptor-α. We observed an upregulation of CB2, 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.

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