Ueda Yuto, Doi Taku, Nagatomo Keiko, Willmore L James, Nakajima Akira
Section of Psychiatry, Department of Clinical Neuroscience, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
Exp Brain Res. 2007 Aug;181(4):571-7. doi: 10.1007/s00221-007-0954-8. Epub 2007 May 8.
We used western blotting to measure the quantity of glutamate and gamma-aminobutyric acid (GABA) transporters proteins within hippocampal tissue obtained from rats who had undergone epileptogenesis. Chronic seizures were induced by amygdalar injection of FeCl(3). We found that the glial glutamate transporters GLAST and GLT-1 were down-regulated at 60 days after initiation of chronic and recurrent seizures. However, the neuronal glutamate transporter EAAC-1 and the GABA transporter GAT-3 were increased. We performed in vivo microdialysis in freely moving animals to estimate in vivo redox state. We found that the hippocampal tissues were oxidized, resulting in even further impairment of glutamate transport. Our data show that epileptogenesis in rats resulting in chronic and recurrent seizures is associated with collapse of glutamate regulation caused by both the molecular down-regulation of glial glutamate transporters combined with the functional failure due to oxidation.
我们采用蛋白质免疫印迹法来测定取自经历癫痫发作形成过程的大鼠海马组织中谷氨酸和γ-氨基丁酸（GABA）转运蛋白的量。通过杏仁核注射氯化铁诱导慢性癫痫发作。我们发现，在慢性复发性癫痫发作开始60天后，胶质细胞谷氨酸转运体GLAST和GLT-1表达下调。然而，神经元谷氨酸转运体EAAC-1和GABA转运体GAT-3表达增加。我们对自由活动的动物进行了体内微透析，以评估体内氧化还原状态。我们发现海马组织被氧化，导致谷氨酸转运功能进一步受损。我们的数据表明，导致大鼠慢性复发性癫痫发作的癫痫发作形成与胶质细胞谷氨酸转运体分子下调以及氧化导致的功能衰竭共同引起的谷氨酸调节功能崩溃有关。
