Background: Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), regulated by AMPK, is an important regulator of mitochondrial fusion. At present, whether the AMPK/PGC-1α signaling pathway regulates mitochondrial dynamics in epileptic rats is still unknown. Methods: Adult male Sprague-Dawley (SD) rats were randomly divided into fourgroups: the control group (0.9% saline, n = 5), the EP groups (lithium-pilocarpine was used to induce epilepsy, and tissues were harvested at 6 and 24 h, every time point, n = 5), the EP + Compound C group (the specific inhibitor of PGC-1α, 15 mg/kg in 2% DMSO, n = 5), and the EP + DMSO group (0.9% saline + 2% DMSO, n = 5). To investigate whether PGC-1α participates in seizures by regulating the expression of mitofusin1/2(MFN1/2)in rats. Results: In this study, the behavioral results indicate that the seizure susceptibility of the rats to epilepsy was increased when the expression of PGC-1α was inhibited. Subsequently, Western blot results suggested that the expression level of both MFN1 and MFN2 in the hippocampus was higher at 6 and 24 h after an epileptic seizure. Besides, the expression of PGC-1α and MFN2 was significantly decreased in the hippocampus when the epileptic rats were treated with Compound C. Furthermore, the immunofluorescence analysis of the localization of MFN1/2 and PGC-1α showed that MFN1/2 was mainly expressed in neurons but not astrocytes in the hippocampus and cerebral cortex of rats. Meanwhile, PGC-1α colocalized with the excitatory post-synaptic marker PSD95, suggesting that PGC-1α may regulate the seizure susceptibility of the rats by mediating excitatory post-synaptic signaling. Conclusion: The AMPK/PGC-1α signaling pathway may play an important role in the lithium-pilocarpine-induced epileptic rat model by mediating the expression of fusion proteins.

背景：受 AMPK 调节的过氧化物酶体增殖物激活受体 γ 辅激活因子-1α (PGC-1α) 是线粒体融合的重要调节因子。目前，AMPK/PGC-1α信号通路是否调控癫痫大鼠线粒体动力学尚不清楚。方法：成年雄性Sprague-Dawley（SD）大鼠随机分为4组：对照组（0.9%生理盐水，n=5）、EP组（锂-毛果芸香碱致癫痫，6、3d取组织） 24 h, 每个时间点, n = 5), EP + Compound C组(PGC-1α特异性抑制剂, 15 mg/kg in 2% DMSO, n = 5), EP + DMSO组(0.9%盐水 + 2% DMSO，n = 5）。探讨PGC-1α是否通过调控大鼠mitofusin1/2(MFN1/2)的表达参与癫痫发作。结果：在本研究中，行为学结果表明，当 PGC-1α 的表达受到抑制时，大鼠对癫痫发作的易感性增加。随后，Western blot 结果表明，癫痫发作后 6 小时和 24 小时海马中 MFN1 和 MFN2 的表达水平较高。此外，化合物C治疗癫痫大鼠后海马区PGC-1α和MFN2的表达显着降低。此外，MFN1/2和PGC-1α定位的免疫荧光分析显示MFN1/2主要表达在神经元中，但在大鼠海马和大脑皮层中没有星形胶质细胞。同时，PGC-1α 与兴奋性突触后标记物 PSD95 共定位，结论： AMPK/PGC-1α信号通路可能通过介导融合蛋白的表达在锂毛果芸香碱致癫痫大鼠模型中发挥重要作用。