Bough Kristopher J, Paquet Maryse, Paré Jean-François, Hassel Bjørnar, Smith Yoland, Hall Randy A, Dingledine Raymond
Department of Pharmacology, Emory University, Atlanta, GA, USA.
Epilepsy Res. 2007 May;74(2-3):232-6. doi: 10.1016/j.eplepsyres.2007.03.002. Epub 2007 Apr 9.
Excessive glutamatergic neurotransmission is considered an underlying factor of epilepsy. Energy-dependent glutamate transporters clear extracellular glutamate to limit neuronal excitability. Evidence suggests that reduced expression and/or activity of glutamate transporters contribute to hyperexcitability and progressive seizure activity in rats. By comparison, treatment with the anticonvulsant ketogenic diet (KD) results in increased mRNA expression of the neuronal glutamate transporter EAAC1, elevated energy reserves, and an increased resistance to seizures in rats. The goal of the current study was to determine whether the expression and/or re-uptake activity of glutamate transporters were elevated in hippocampal tissue of rats after KD treatment. Rats were fed either a ketogenic- or control diet for 4-5 weeks. Western blot analysis showed that protein levels of EAAC1, GLT-1 and GLAST glutamate transporters were not changed in hippocampus, cerebral cortex, or cerebellum after KD. Electron microscopic evidence indicated that the KD did not affect hippocampal EAAC1 distribution. In addition, the re-uptake activity of (3)H-glutamate into hippocampal proteoliposomes was similar in both KD and control tissue extracts. These multiple studies suggest that the anticonvulsant nature of the KD does not stem from enhanced glutamate re-uptake.
谷氨酸能神经传递过度被认为是癫痫的一个潜在因素。能量依赖性谷氨酸转运体清除细胞外谷氨酸以限制神经元兴奋性。有证据表明，谷氨酸转运体表达降低和/或活性降低会导致大鼠的过度兴奋和进行性癫痫活动。相比之下，用抗惊厥生酮饮食（KD）治疗可导致大鼠神经元谷氨酸转运体EAAC1的mRNA表达增加、能量储备升高以及对癫痫的抵抗力增强。本研究的目的是确定KD治疗后大鼠海马组织中谷氨酸转运体的表达和/或再摄取活性是否升高。给大鼠喂食生酮饮食或对照饮食4-5周。蛋白质印迹分析表明，KD后海马、大脑皮层或小脑中EAAC1、GLT-1和GLAST谷氨酸转运体的蛋白质水平没有变化。电子显微镜证据表明，KD不影响海马EAAC1的分布。此外，在KD和对照组织提取物中，（3）H-谷氨酸进入海马蛋白脂质体的再摄取活性相似。这些多项研究表明，KD的抗惊厥性质并非源于谷氨酸再摄取增强。
