Khaksar Sepideh, Salimi Mona, Zeinoddini Hadi, Naderi Nima
Department of Plant Sciences, Biological Sciences, Alzahra University, Tehran, Iran.
Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.
Neurochem Res. 2022 May;47(5):1226-1242. doi: 10.1007/s11064-021-03517-5. Epub 2022 Feb 3.
In this research, the involvement of CB1 and TRPV1 receptors in the possible protective effects of anandamide were investigated in the kindling model of epilepsy. The basolateral amygdala of the rat brain was chosen to put stimulating electrodes. Semi-rapid kindling was induced by a repetitive sub-threshold stimulation for 5-9 consecutive days. There were seven groups, six of which were kindled and used for drug testing by intracerebroventricular (i.c.v.) microinjection. (i) Sham, (ii) control group received vehicles, (iii) anandamide (AEA; 100 ng/rat), (iv) capsazepine (TRPV1 antagonist; 100 ng/rat), (v) AM251 (CB1 antagonist; 100 ng/rat), (vi) AM251 + anandamide, and (vii) capsazepine + anandamide. The after-discharge duration, seizure duration, and stage five duration were measured in rats. Moreover, the expressions of the extracellular signal-regulated kinase (ERK) and the cAMP responsive element binding (CREB) proteins in the hippocampus were also studied. The anandamide-treated group showed a significant decrease in seizure scores, while no change was shown in seizure scores in the capsazepine- and AM251-treated groups compared with the control group. Co-administrations of either capsazepine + AEA or AM251 + AEA attenuated the protective effect of AEA against seizure. Furthermore, the group received AEA showed a decrease in the expressions of CREB and p-CREB possibly through the activation of the CB1 and TRPV1 receptors. Activation of CB1 and TRPV1 receptors might be involved in AEA anticonvulsant effect in kindling model of epilepsy. This effect could be due to suppression of CREB phosphorylation in hippocampal neurons.
在本研究中，在癫痫点燃模型中研究了CB1和TRPV1受体在花生四烯酸乙醇胺可能的保护作用中的参与情况。选择大鼠脑的基底外侧杏仁核放置刺激电极。通过连续5 - 9天的重复性阈下刺激诱导半快速点燃。实验分为七组，其中六组进行点燃并通过脑室内（i.c.v.）微量注射进行药物测试。（i）假手术组，（ii）对照组注射溶剂，（iii）花生四烯酸乙醇胺（AEA；100 ng/大鼠），（iv）辣椒素（TRPV1拮抗剂；100 ng/大鼠），（v）AM251（CB1拮抗剂；100 ng/大鼠），（vi）AM251 + 花生四烯酸乙醇胺，以及（vii）辣椒素 + 花生四烯酸乙醇胺。测量大鼠的后放电持续时间、癫痫发作持续时间和五级发作持续时间。此外，还研究了海马中细胞外信号调节激酶（ERK）和cAMP反应元件结合蛋白（CREB）的表达。花生四烯酸乙醇胺处理组的癫痫发作评分显著降低，而与对照组相比，辣椒素和AM251处理组的癫痫发作评分没有变化。辣椒素 + AEA或AM251 + AEA联合给药减弱了AEA对癫痫发作的保护作用。此外，接受AEA的组可能通过激活CB1和TRPV1受体使CREB和p-CREB的表达降低。CB1和TRPV1受体的激活可能参与了花生四烯酸乙醇胺在癫痫点燃模型中的抗惊厥作用。这种作用可能是由于海马神经元中CREB磷酸化的抑制。
