Peterson Allison R, Binder Devin K
Division of Biomedical Sciences, Center for Glial-Neuronal Interactions, School of Medicine, University of California, Riverside, Riverside, CA, United States.
Front Neurol. 2020 Sep 8;11:1006. doi: 10.3389/fneur.2020.01006. eCollection 2020.
Astrocytes regulate and respond to extracellular glutamate levels in the central nervous system (CNS) the Na-dependent glutamate transporters glutamate transporter-1 (GLT-1) and glutamate aspartate transporter (GLAST) and the metabotropic glutamate receptors (mGluR) 3 and mGluR5. Both impaired astrocytic glutamate clearance and changes in metabotropic glutamate signaling could contribute to the development of epilepsy. Dysregulation of astrocytic glutamate transporters, GLT-1 and GLAST, is a common finding across patients and preclinical seizure models. Astrocytic metabotropic glutamate receptors, particularly mGluR5, have been shown to be dysregulated in both humans and animal models of temporal lobe epilepsy (TLE). In this review, we synthesize the available evidence regarding astrocytic glutamate homeostasis and astrocytic mGluRs in the development of epilepsy. Modulation of astrocyte glutamate uptake and/or mGluR activation could lead to novel glial therapeutics for epilepsy.
星形胶质细胞调节并响应中枢神经系统（CNS）中的细胞外谷氨酸水平，即钠依赖性谷氨酸转运体谷氨酸转运体-1（GLT-1）和谷氨酸天冬氨酸转运体（GLAST），以及代谢型谷氨酸受体（mGluR）3和mGluR5。星形胶质细胞对谷氨酸的清除受损以及代谢型谷氨酸信号传导的改变都可能导致癫痫的发生。星形胶质细胞谷氨酸转运体GLT-1和GLAST的失调在患者和临床前癫痫发作模型中都很常见。星形胶质细胞代谢型谷氨酸受体，尤其是mGluR5，在颞叶癫痫（TLE）的人类和动物模型中均显示失调。在这篇综述中，我们综合了关于癫痫发生过程中星形胶质细胞谷氨酸稳态和星形胶质细胞mGluR的现有证据。调节星形胶质细胞对谷氨酸的摄取和/或mGluR激活可能会带来治疗癫痫的新型神经胶质疗法。
