GPR120 modulates epileptic seizure and neuroinflammation mediated by NLRP3 inflammasome

Abstract

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-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-1β signaling pathway.

Mitochondrial ferritin alleviates ferroptosis in a kainic acid‐induced mouse epilepsy model by regulating iron homeostasis: Involvement of nuclear factor erythroid 2‐related factor 2

“…Immunofluorescence methods have been widely described. 41 Briefly, 10 μm thick tissue slices were fixed in methanol for 30 min, washed three times in phosphate‐buffered saline (PBS), cleaved with 0.3% Triton X‐100 for 5 min, and mounted in 10% donkey serum working solution (Boster Biological Technology, Wuhan, China) for 60 min. The sliced and mixed samples were incubated with primary antibodies for 12 h at 4°C.…”

“…The mouse model of KA‐induced epilepsy has been widely reported 41 . The mouse model of KA‐induced epilepsy was established 21 days after injection of AAV.…”

“…The mouse model of KA-induced epilepsy has been widely reported. 41 The mouse model of KA-induced epilepsy was established 21 days after injection of AAV. The mice were anesthetized with pentobarbital sodium (50 mg/kg) via intraperitoneal injection and then se- Mice injected with KA by stereotactic placement are placed under a video surveillance system to record seizures at 3, 7, 14, and 28 days.…”

The inhibition of PGAM5 suppresses seizures in a kainate-induced epilepsy model via mitophagy reduction

“…Nissl staining was performed as described previously ( Qin et al, 2022 ). Paraffin-embedded sections were dewaxed with 0.5% cresyl violet at room temperature (RT), hydrated, and stained with Nissl dye at RT for 10 min.…”

“…Immunofluorescence staining was performed as previously described ( Qin et al, 2022 ). After anesthesia, mice were rapidly decapitated, and the brains were immediately postfixed in 4% paraformaldehyde for 24 h at 4°C.…”