Aso Ester, Andrés-Benito Pol, Grau-Escolano Jordi, Caltana Laura, Brusco Alicia, Sanz Pascual, Ferrer Isidre
Unitat de Farmacologia, Departament de Patologia i Terapèutica Experimental, Facultat de Medicina i Ciències de la Salut, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Spain.
Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
Cannabis Cannabinoid Res. 2020 Jun 5;5(2):150-163. doi: 10.1089/can.2019.0005. eCollection 2020 Jun 1.
Lafora disease (LD) is a rare form of progressive infantile epilepsy in which rapid neurological deterioration occurs as the disease advances, leading the patients to a vegetative state and then death, usually within the first decade of disease onset. Based on the capacity of the endogenous cannabinoid system (ECS) to modulate several cellular processes commonly altered in many neurodegenerative processes, as well as the antiepileptic properties of certain natural cannabinoids, the aim of this study was to evaluate the role of the ECS in LD progression. We tested whether a natural cannabis extract highly enriched in cannabidiol (CBD) might be effective in curbing the pathological phenotype of malin knockout (KO) mice as an animal model of LD. Our results reveal for the first time that alterations in the ECS occur during the evolution of LD, mainly at the level of CB, CB, and G protein-coupled receptor 55 (GPR55) receptor expression, and that a CBD-enriched extract (CBDext) is able to reduce the cognitive impairment exhibited by malin KO mice. However, in contrast to what has previously been reported for other kinds of refractory epilepsy in childhood, the CBD-enriched extract does not reduce the severity of the epileptic seizures induced in this animal model of LD. In summary, this study reveals that the ECS might play a role in LD and that a CBD-enriched extract partially reduces the dementia-like phenotype, but not the increased vulnerability to epileptic seizures, exhibited by an animal model of such a life-threatening disease.
拉福拉病（LD）是一种罕见的进行性婴儿癫痫，随着疾病进展会出现快速的神经功能恶化，导致患者进入植物人状态，然后死亡，通常在疾病发作的第一个十年内。基于内源性大麻素系统（ECS）调节许多神经退行性过程中常见的几种细胞过程的能力，以及某些天然大麻素的抗癫痫特性，本研究的目的是评估ECS在LD进展中的作用。我们测试了一种高度富含大麻二酚（CBD）的天然大麻提取物是否能有效抑制作为LD动物模型的malin基因敲除（KO）小鼠的病理表型。我们的结果首次揭示，在LD的发展过程中，ECS会发生改变，主要是在CB1、CB2和G蛋白偶联受体55（GPR55）受体表达水平，并且富含CBD的提取物（CBDext）能够减轻malin KO小鼠表现出认知障碍。然而，与先前关于儿童期其他类型难治性癫痫的报道不同，富含CBD的提取物并不能降低在这个LD动物模型中诱发的癫痫发作的严重程度。总之，本研究表明ECS可能在LD中起作用，并且富含CBD的提取物部分减轻了类似痴呆的表型，但没有减轻这种危及生命疾病的动物模型所表现出的癫痫发作易感性增加。
