Ueda Y, Doi T, Tokumaru J, Yokoyama H, Nakajima A, Mitsuyama Y, Ohya-Nishiguchi H, Kamada H, Willmore L J
Department of Psychiatry, Miyazaki Medical College, Miyazaki, Japan.
J Neurochem. 2001 Feb;76(3):892-900. doi: 10.1046/j.1471-4159.2001.00087.x.
We used northern and western blotting to measure the quantity of glutamate and GABA transporters mRNA and their proteins within the hippocampal tissue of rats with epileptogenesis. Chronic seizures were induced by amygdalar injection of kainic acid 60 days before death. We found that expression of the mRNA and protein of the glial glutamate transporters GLAST and GLT-1 were down-regulated in the kainic acid-administered group. In contrast, EAAC-1 and GAT-3 mRNA and their proteins were increased, while GAT-1 mRNA and protein were not changed. We performed in vivo microdialysis in the freely moving state. During the interictal state, the extracellular glutamate concentration was increased, whereas the GABA level was decreased in the kainic acid group. Following potassium-induced depolarization, glutamate overflow was higher and the recovery time to the basal release was prolonged in the kainic acid group relative to controls. Our data suggest that epileptogenesis in rats with kainic acid-induced chronic seizures is associated with the collapse of extracellular glutamate regulation caused by both molecular down-regulation and functional failure of glutamate transport.
我们采用Northern印迹法和Western印迹法来测定致痫大鼠海马组织中谷氨酸和γ-氨基丁酸（GABA）转运体的mRNA及其蛋白的量。在处死前60天，通过杏仁核注射海藻酸诱导大鼠发生慢性癫痫发作。我们发现，给予海藻酸的组中，胶质细胞谷氨酸转运体GLAST和GLT-1的mRNA及蛋白表达下调。相反，EAAC-1和GAT-3的mRNA及其蛋白增加，而GAT-1的mRNA和蛋白未发生变化。我们在自由活动状态下进行了体内微透析。在发作间期，海藻酸组的细胞外谷氨酸浓度升高，而GABA水平降低。相对于对照组，在海藻酸组中，钾离子诱导去极化后，谷氨酸溢出更高，且恢复至基础释放水平的时间延长。我们的数据表明，海藻酸诱导的慢性癫痫发作大鼠的致痫过程与谷氨酸转运体分子下调和功能衰竭所导致的细胞外谷氨酸调节功能崩溃有关。
