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首页> 外文期刊>The European Journal of Neuroscience >Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide.
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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.

机译：在多发性硬化症病毒模型中研究内源性大麻素系统的研究揭示了棕榈酰乙醇酰胺的治疗作用。

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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.
机译：大麻素最近已被批准用于治疗多发性硬化症（MS）的疼痛。来自动物研究的越来越多的证据表明，这类化合物还可以有效对抗这种病理学中发生的神经变性，脱髓鞘，炎症和自身免疫过程。但是，大麻素的使用受到其心理作用的限制。在这种情况下，内源性大麻素信号转导的增强可以代表使用外源性大麻素配体的替代品。在这里，我们研究了内源性大麻素系统不同元素在小鼠MS慢性模型中的表达。我们首先研究了两种大麻素受体CB（1）和CB（2）的表达，以及推定的细胞内大麻素受体过氧化物酶体增殖物激活受体α的表达。我们观察到MS模型发作后60天，CB（2）的上调与促炎细胞因子的产生有关。这时，内源性大麻素，2-花生四烯酸甘油酯和抗炎性anandamide同源物，palmthothoylethanolamide的水平增加了，而anandamide的水平没有变化。这些变化不是由于此时（60天）的降解酶，脂肪酸酰胺水解酶和单酰基甘油脂酶或生物合成酶，二酰基甘油脂酶-α和N-酰基磷脂酰乙醇胺磷脂酶-D的表达差异引起的。最后，外源施用棕榈酰乙醇酰胺导致患有这种MS模型的动物的运动障碍减少，并伴有抗炎作用。这项研究总体上突出了内源性大麻素在MS中的潜在治疗作用。

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