As a neurological disorder, epilepsy has affected over 65 million people all over the world because of the unforeseeable seizures it might cause. However, in-depth understandings of the pathogenesis of epilepsy and effective treatments for the disease are still lacked. Recent discoveries suggest that autophagy, as an endogenous self-cleansing pathway in mammals, might be involved in the onset of epilepsy. Our study assumes that a non-histone DNA binding protein, high mobility group box-1 (HMGB1), formerly considered as a crucial inflammatory factor, may mediate the autophagy of neurons in epileptic mouse brain. To verify this hypothesis, pilocarpine induced epilepsy mouse model was constructed. The mice were treated with HMGB1 antibody for 4 weeks after the initial epileptic seizure. Behavioral test results suggested a recovery of learning ability and memory in epileptic mice when treated with HMGB1 antibody. Pathological changes in hippocampus were inspected under microscopes and hippocampus damages caused by seizures in mouse with epilepsy such as increased intracellular space were alleviated by HMGB1 antibody treatment. Moreover, the expressions of the proteins involved in autophagy pathways were detected by immunofluorescence staining and western blot. microtubule-associated protein 1A/1B-light chain 3 (LC3), Beclin 1, autophagy protein-5 (ATG5), and ATG7 levels were significantly decreased by HMGB1 antibody while the level of p62 was increased. TdT-mediated dUTP Nick-End Labeling (TUNEL) illustrated that cell apoptosis induced by seizures in hippocampus was mitigated by HMGB1 antibody. In conclusion, we propose that HMGB1 may induce increased autophagy in epilepsy mouse model.

中文翻译：

---

高迁移率族框 1 抗体抑制自噬并减轻毛果芸香碱诱导的小鼠癫痫模型中的海马损伤。

作为一种神经系统疾病，癫痫症已经影响了全世界超过 6500 万人，因为它可能会导致不可预见的癫痫发作。然而，对于癫痫的发病机制和对该病的有效治疗仍缺乏深入的认识。最近的发现表明，自噬作为哺乳动物的一种内源性自我清洁途径，可能与癫痫的发生有关。我们的研究假设非组蛋白 DNA 结合蛋白、高迁移率族框 1 (HMGB1)，以前被认为是一种关键的炎症因子，可能介导癫痫小鼠大脑中神经元的自噬。为了验证这一假设，构建了毛果芸香碱诱发的癫痫小鼠模型。在最初的癫痫发作后，小鼠用 HMGB1 抗体治疗 4 周。行为测试结果表明，当用 HMGB1 抗体治疗时，癫痫小鼠的学习能力和记忆力有所恢复。在显微镜下观察海马的病理变化，HMGB1抗体治疗减轻癫痫小鼠癫痫发作引起的海马损伤，如细胞内间隙增加。此外，通过免疫荧光染色和蛋白质印迹检测参与自噬途径的蛋白质的表达。HMGB1 抗体显着降低了微管相关蛋白 1A/1B-轻链 3 (LC3)、Beclin 1、自噬蛋白 5 (ATG5) 和 ATG7 的水平，同时增加了 p62 的水平。TdT 介导的 dUTP 缺口末端标记 (TUNEL) 表明 HMGB1 抗体减轻了海马癫痫发作诱导的细胞凋亡。综上所述，