GPR120 modulates epileptic seizure and neuroinflammation mediated by NLRP3 inflammasome

作者全名："Qin, Zhangjin; Song, Jiaqi; Lin, Aolei; Yang, Wei; Zhang, Wenbo; Zhong, Fuxin; Huang, Lihong; Lu, Yang; Yu, Weihua"

作者地址："[Qin, Zhangjin; Song, Jiaqi; Zhong, Fuxin; Huang, Lihong; Yu, Weihua] Chongqing Med Univ, Inst Neurosci, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Lin, Aolei] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Neurol, Dept Neurol, Chongqing 400016, Peoples R China; [Yang, Wei] Chongqing Med Univ, Affiliated Hosp 1, Dept Integrated Tradit Chinese Med & Western Med, Chongqing 400016, Peoples R China; [Zhang, Wenbo; Lu, Yang] Chongqing Med Univ, Affiliated Hosp 1, Dept Geriatr, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Yu, WH (通讯作者)，Chongqing Med Univ, Inst Neurosci, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Lu, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Geriatr, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：JOURNAL OF NEUROINFLAMMATION

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000800839400005

JCR分区：Q1

影响因子：9.3

年份：2022

卷号：19

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：GPR120; Neuroinflammation; NLRP3 inflammasome; Epilepsy; Neuronal damage

摘要："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-1 beta, IL-6, IL-18, and pyrin domain-containing protein 3 (NLRP3) inflammasome, whereas knockdown GPR120 showed the opposite effect. The effects of GPR120 knockdown were reversed by VX765 inhibition cysteinyl aspartate specific proteinase-1 (Caspase-1). Conclusion GPR120 modulates epileptic seizure activity and affects neuronal survival in KA-induced mouse model of temporal lobe epilepsy. Furthermore, GPR120 regulated neuroinflammation in epileptic animals through NLRP3/Caspase-1/IL-1 beta signaling pathway."

基金机构："National Natural Science Foundation of China [81871019, 81671286]"

基金资助正文："This study was supported by Grants from the National Natural Science Foundation of China (81871019, 81671286)."