Department of Pediatrics, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian 350001, China.
Department of Pediatrics, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian 350001, China.
Brain Res Bull. 2024 Oct 15;217:111057. doi: 10.1016/j.brainresbull.2024.111057. Epub 2024 Aug 28.
Epilepsy with recurrent seizures is characterized by neuronal damage and glial proliferation induced by brain inflammation. Recurrent seizures can lead to changes in the microRNA (miRNA) spectrum, significantly influencing the inflammatory response of microglia. MiR-155-5p, as a pro-inflammatory miRNA, is increased in the epileptic brain. However, its specific role in acute seizures remains unknown. The study aimed to develop a new strategy for treating epilepsy by investigating how silencing of miR-155-5p initiated its anticonvulsive mechanism. The level of miR-155-5p was up-regulated in the hippocampus of epileptic immature rats induced by kainic acid (KA). The use of antago-miR-155-5p exerted significant beneficial effects on the seizure scores, brain discharges and cognition in immature rats following KA-induced epilepsy. Antago-miR-155-5p also inhibited neuron damage and microglial activation. Moreover, the silencing of miR-155-5p significantly inhibited the Dual-specificity phosphatase 14 (Dusp14)/ mitogen-activated protein kinase (MAPK) axis in vivo. MiR-155-5p interacted with dusp14 to regulate MAPK signaling way expression, verified by a dual-luciferase reporter assay. The results suggested that the silencing of miR-155-5p might reduce hippocampal damage in epileptic immature rats induced by KA via Dusp14/MAPK signaling way. This implied that miR-155-5p could serve as a therapeutic tool to prevent the development of epilepsy.
癫痫伴反复发作的特征是神经元损伤和星形胶质细胞增殖，这是由脑炎症引起的。反复发作可导致 microRNA（miRNA）谱发生变化，显著影响小胶质细胞的炎症反应。miR-155-5p 作为一种促炎 miRNA，在癫痫脑中增加。然而，其在急性发作中的具体作用尚不清楚。本研究旨在通过研究沉默 miR-155-5p 如何引发其抗惊厥机制，为治疗癫痫开发一种新策略。在红藻氨酸（KA）诱导的癫痫未成熟大鼠的海马体中，miR-155-5p 的水平上调。使用抗 miR-155-5p 在 KA 诱导的癫痫后对未成熟大鼠的癫痫发作评分、脑放电和认知产生显著有益的影响。抗 miR-155-5p 还抑制神经元损伤和小胶质细胞激活。此外，miR-155-5p 的沉默在体内显著抑制了双特异性磷酸酶 14（Dusp14）/丝裂原活化蛋白激酶（MAPK）轴。miR-155-5p 通过双荧光素酶报告基因检测与 dusp14 相互作用，调节 MAPK 信号通路的表达，验证了这一结果。结果表明，沉默 miR-155-5p 可能通过 Dusp14/MAPK 信号通路减少 KA 诱导的癫痫未成熟大鼠海马体损伤。这表明 miR-155-5p 可作为预防癫痫发生的治疗工具。
