Rocha Luisa, Cinar Resat, Guevara-Guzmán Rosalinda, Alonso-Vanegas Mario, San-Juan Daniel, Martínez-Juárez Iris, Castañeda-Cabral José Luis, Carmona-Cruz Francia
Department of Pharmacobiology, Center of Research and Advanced Studies, Mexico City, Mexico.
Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, United States.
Front Behav Neurosci. 2020 May 6;14:52. doi: 10.3389/fnbeh.2020.00052. eCollection 2020.
Experimental evidence points out that the activation of the endocannabinoid system induces neuroprotective effects and reduces mood disorders. In the hippocampus of patients with mesial temporal lobe epilepsy (MTLE), studies indicated augmented cannabinoid 1 receptor (CBR) binding, in spite of its low mRNA and protein expressions. Although this situation suggests an enhanced CBR-induced neurotransmission in patients with MTLE, especially those with pharmacoresistant seizures, which present important neuronal damage and high comorbid mood disorders. The present study focused to investigate the status of CBR and the endocannabinoid system by obtaining CBR-induced G-protein signaling efficacy and measuring the tissue levels of endocannabinoids in the hippocampus and the temporal neocortex of patients with pharmacoresistant MTLE. Furthermore, the obtained results were correlated with comorbid anxiety and depression. The experiments revealed that patients with MTLE present increased CBR-induced G-protein signaling efficacy (Emax) as well as an augmented tissue content of anandamide and oleoylethanolamine and low 2-arachidonoylglycerol. Some of these changes were more evident in patients with MTLE without mood disorders. The current findings indicate that pharmacoresistant MTLE is associated with increased CBR-induced transductional mechanisms as well as augmented tissue content of specific endocannabinoids in the hippocampus and the temporal neocortex. The enhanced endocannabinoid neurotransmission may be involved in the absence of comorbid mood disorders in some patients with MTLE.
实验证据表明，内源性大麻素系统的激活具有神经保护作用，并可减轻情绪障碍。在颞叶内侧癫痫（MTLE）患者的海马体中，研究表明大麻素1受体（CBR）结合增加，尽管其mRNA和蛋白质表达水平较低。尽管这种情况表明MTLE患者，尤其是那些药物难治性癫痫患者中CBR诱导的神经传递增强，这些患者存在重要的神经元损伤和高度共病的情绪障碍。本研究旨在通过获得CBR诱导的G蛋白信号传导效能，并测量药物难治性MTLE患者海马体和颞叶新皮质中内源性大麻素的组织水平，来研究CBR和内源性大麻素系统的状态。此外，将获得的结果与共病的焦虑和抑郁进行关联。实验表明，MTLE患者CBR诱导的G蛋白信号传导效能（Emax）增加，同时花生四烯酸乙醇胺和油酰乙醇胺的组织含量增加，而2-花生四烯酸甘油酯含量降低。其中一些变化在无情绪障碍的MTLE患者中更为明显。目前的研究结果表明，药物难治性MTLE与海马体和颞叶新皮质中CBR诱导的转导机制增加以及特定内源性大麻素的组织含量增加有关。内源性大麻素神经传递增强可能与一些MTLE患者无共病情绪障碍有关。
