Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Department of Psychiatry, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Department of Physiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Cell Rep Med. 2023 May 16;4(5):101020. doi: 10.1016/j.xcrm.2023.101020. Epub 2023 Apr 19.
The excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) contribute to epileptogenesis. Thirty patients with epilepsy and 31 healthy controls are scanned using positron emission tomography with our recently developed radiotracer for AMPARs, [C]K-2, which measures the density of cell-surface AMPARs. In patients with focal-onset seizures, an increase in AMPAR trafficking augments the amplitude of abnormal gamma activity detected by electroencephalography. In contrast, patients with generalized-onset seizures exhibit a decrease in AMPARs coupled with increased amplitude of abnormal gamma activity. Patients with epilepsy had reduced AMPAR levels compared with healthy controls, and AMPARs are reduced in larger areas of the cortex in patients with generalized-onset seizures compared with those with focal-onset seizures. Thus, epileptic brain function can be regulated by the enhanced trafficking of AMPAR due to Hebbian plasticity with increased simultaneous neuronal firing and compensational downregulation of cell-surface AMPARs by the synaptic scaling.
兴奋性谷氨酸 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPARs）参与癫痫发生。使用我们最近开发的 AMPAR 放射性示踪剂 [C]K-2 对 30 例癫痫患者和 31 名健康对照者进行正电子发射断层扫描，该示踪剂测量细胞表面 AMPAR 的密度。在局灶性发作性癫痫患者中，AMPAR 转运的增加增强了脑电图检测到的异常伽马活动的幅度。相比之下，全身性发作性癫痫患者表现出 AMPAR 的减少伴随着异常伽马活动幅度的增加。与健康对照组相比，癫痫患者的 AMPAR 水平降低，与局灶性发作性癫痫患者相比，全身性发作性癫痫患者的皮质更大区域的 AMPAR 减少。因此，癫痫脑功能可以通过赫布可塑性增强 AMPAR 的转运来调节，这种可塑性表现为同时神经元放电增加，以及通过突触缩放对细胞表面 AMPAR 进行代偿性下调。
