GPR120 modulates epileptic seizure and neuroinflammation mediated by NLRP3 inflammasome

作者：Zhangjin Qin, Jiaqi Song, Aolei Lin, Wei Yang, Wenbo Zhang, Fuxin Zhong, Lihong Huang, Yang Lü, Weihua Yu · 发表于：Journal of Neuroinflammation · 年份：2022 · DOI：10.1186/s12974-022-02482-2 · 被引用次数：69 · 研究领域：Epilepsy research and treatment、Inflammasome and immune disorders、S100 Proteins and Annexins

BACKGROUND: The complex pathophysiology of epilepsy hampers the development of effective treatments. Although more than ten kinds of anti-seizures drugs (ASDs) have good effects on seizure control worldwide, about 30% of patients still display pharmacoresistance against ASDs. Neuroinflammation seems to play a crucial role in disease progression. G protein-coupled receptor 120 (GPR120) has been shown to negatively regulate inflammation and apoptosis. However, the role of GPR120 in epilepsy remains unclear. In this study, we aimed to explore the mechanism of GPR120 in epilepsy. METHODS: Male adult C57BL/6 mice were intracranially injected with kainic acid (KA) to establish epilepsy model, and the adeno associated virus (AAV) was administered intracranially at 3 weeks before KA injection. VX765 was administered by intragastric administration at 30 min before KA induced and an equal dose administrated twice a day (10 a.m. and 4 p.m.) lasting 7 days until the mice were killed. Western blot analysis, immunofluorescence staining, video monitoring of seizure, LFP recording, Nissl staining were performed. RESULTS: GPR120 was increased in both the hippocampus and cortex in the KA-induced model with temporal lobe epilepsy (TLE), and both were most highly expressed at 7 days after KA injection. Overexpression of GPR120 significantly alleviated epileptic activity, reduced neuronal death after status epilepticus (SE), downregulated the expression of IL-1β, IL-6, IL-18, and pyrin domain-con...