内质网(ER)与许多细胞功能有关,从转录后修饰到蛋白质的正确折叠,这些功能的破坏会导致ER压力。虽然癫痫发作与内质网应激的关系已有报道,ER应激途径对癫痫发生的贡献尚不清楚.本研究旨在探讨由温和和高剂量Thapsigargin(Tg)调节的ER应激相关分子途径对无癫痫活动的可能影响。CACNA1H与WAG/Rij大鼠的免疫应答。为此,大鼠分为四组;轻度剂量(20ng)Tg,高剂量(200ng)Tg,盐水,和DMSO和脑室内给药的药物。在基线记录后,在给药后1小时和24小时记录EEG活性。在皮质和丘脑组织中,GRP78,ERp57,GAD153蛋白变化(WesternBlot),Eif2ak3,XBP-1,ATF6,CACNA1HmRNA表达(RT-PCR),检测NF-κB和TNF-α水平(ELISA)。与给予盐水相比,轻度剂量Tg给药导致第24小时的尖峰波放电(SWD)活性增加,和高剂量Tg,它也显着增加了GRP78蛋白的量,Eif2ak3、XBP-1和CACNA1HmRNA在丘脑组织中的表达。相比之下,高剂量Tg给药抑制SWD活性,并显着增加丘脑中XBP-1和ATF6mRNA的表达,并增加NF-κB和TNF-α水平。总之,我们的研究结果表明,Tg通过调节未折叠蛋白反应途径和以剂量依赖的方式激活炎症过程来影响SWD的发生.
The Endoplasmic Reticulum (ER) is associated with many cellular functions, from post-transcriptional modifications to the proper folding of proteins, and disruption of these functions causes ER stress. Although the relationship between epileptic seizures and ER stress has been reported, the contribution of ER stress pathways to epileptogenesis is still unclear. This study aimed to investigate the possible effects of ER stress-related molecular pathways modulated by mild- and high-dose
Thapsigargin (Tg) on absence epileptic activity, CACNA1H and immune responses in WAG/Rij rats. For this purpose, rats were divided into four groups; mild-dose (20 ng) Tg, high-dose (200 ng) Tg, saline, and DMSO and drugs administered intracerebroventriculary. EEG activity was recorded for 1 h and 24 h after drug administration following the baseline recording. In cortex and thalamus tissues, GRP78, ERp57, GAD153 protein changes (Western Blot), Eif2ak3, XBP-1, ATF6, CACNA1H mRNA expressions (RT-PCR), NF-κB and TNF-α levels (ELISA) were measured. Mild-dose-Tg administration resulted in increased spike-wave discharge (SWD) activity at the 24th hour compared to administration of saline, and high-dose-Tg and it also significantly increased the amount of GRP78 protein, the expression of Eif2ak3, XBP-1, and CACNA1H mRNA in the thalamus tissue. In contrast, high-dose-Tg administration suppressed SWD activity and significantly increased XBP-1 and ATF6 mRNA expression in the thalamus, and increased NF-κB and TNF-α levels. In conclusion, our findings indicate that Tg affects SWD occurrence by modulating the unfolded protein response pathway and activating inflammatory processes in a dose-dependent manner.