Epilepsy is a common neurological disease, and approximately 30% of patients do not respond adequately to antiepileptic drug treatment. Recent studies suggest that G protein-coupled receptor 40 (GPR40) is expressed in the central nervous system and is involved in the regulation of neurological function. However, the impact of GPR40 on epileptic seizures remains unclear. In this study, we first reported that GPR40 expression was increased in epileptic brains. In the kainic acid-induced epilepsy model, GPR40 activation after status epilepticus alleviated epileptic activity, whereas GPR40 inhibition showed the opposite effect. In the pentylenetetrazole-induced kindling model, susceptibility to epilepsy was reduced with GPR40 activation and increased with GPR40 inhibition. Whole-cell patch-clamp recordings demonstrated that GPR40 affected N-methyl-d-aspartate (NMDA) receptor-mediated synaptic transmission. Moreover, GPR40 regulated NR2A and NR2B expression on the surface of neurons. In addition, endocytosis of NMDA receptors and binding of GPR40 with NR2A and NR2B can be regulated by GPR40. Together, our findings indicate that GPR40 modulates epileptic seizures, providing a novel antiepileptic target.

中文翻译：

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GPR40调节癫痫发作和NMDA受体功能。

癫痫病是一种常见的神经系统疾病，大约30％的患者对抗癫痫药治疗没有足够的反应。最近的研究表明，G蛋白偶联受体40（GPR40）在中枢神经系统中表达，并参与神经功能的调节。但是，GPR40对癫痫发作的影响尚不清楚。在这项研究中，我们首先报道了癫痫大脑中GPR40的表达增加了。在海藻酸诱导的癫痫模型中，癫痫持续状态后的GPR40激活减轻了癫痫活性，而对GPR40的抑制则表现出相反的作用。在戊四唑诱导的点燃模型中，对癫痫的敏感性随着GPR40的激活而降低，而随着GPR40的抑制而增加。全细胞膜片钳记录表明GPR40受到影响N-甲基-d-天冬氨酸（NMDA）受体介导的突触传递。此外，GPR40调节神经元表面上的NR2A和NR2B表达。另外，NMDA受体的内吞作用和GPR40与NR2A和NR2B的结合可以由GPR40调节。在一起，我们的发现表明，GPR40调节癫痫发作，提供一个新的抗癫痫的目标。