海马体和新皮质癫痫中神经元谷氨酸转运体（EAAT3/EAAC1）表达增加。
Increased expression of the neuronal glutamate transporter (EAAT3/EAAC1) in hippocampal and neocortical epilepsy.
作者信息
Crino Peter B, Jin Hong, Shumate Melissa D, Robinson Michael B, Coulter Douglas A, Brooks-Kayal Amy R
机构信息
PENN Epilepsy Center, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
出版信息
Epilepsia. 2002 Mar;43(3):211-8. doi: 10.1046/j.1528-1157.2002.35001.x.
PURPOSE
To define the changes in gene and protein expression of the neuronal glutamate transporter (EAAT3/EAAC1) in a rat model of temporal lobe epilepsy as well as in human hippocampal and neocortical epilepsy.
METHODS
The expression of EAAT3/EAAC1 mRNA was measured by reverse Northern blotting in single dissociated hippocampal dentate granule cells from rats with pilocarpine-induced temporal lobe epilepsy (TLE) and age-matched controls, in dentate granule cells from hippocampal surgical specimens from patients with TLE, and in dysplastic neurons microdissected from human focal cortical dysplasia specimens. Immunolabeling of rat and human hippocampi and cortical dysplasia tissue with EAAT3/EAAC1 antibodies served to corroborate the mRNA expression analysis.
RESULTS
The expression of EAAT3/EAAC1 mRNA was increased by nearly threefold in dentate granule cells from rats with spontaneous seizures compared with dentate granule cells from control rats. EAAT3/EAAC1 mRNA levels also were high in human dentate granule cells from patients with TLE and were significantly elevated in dysplastic neurons in cortical dysplasia compared with non-dysplastic neurons from postmortem control tissue. No difference in expression of another glutamate transporter, EAAT2/GLT-1, was observed. Immunolabeling demonstrated that EAAT3/EAAC1 protein expression was enhanced in dentate granule cells from both rats and humans with TLE as well as in dysplastic neurons from human cortical dysplasia tissue.
CONCLUSIONS
Elevations of EAAT3/EAAC1 mRNA and protein levels are present in neurons from hippocampus and neocortex in both rats and humans with epilepsy. Upregulation of EAAT3/EAAC1 in hippocampal and neocortical epilepsy may be an important modulator of extracellular glutamate concentrations and may occur as a response to recurrent seizures in these cell types.
目的
确定在颞叶癫痫大鼠模型以及人类海马和新皮质癫痫中神经元谷氨酸转运体（EAAT3/EAAC1）的基因和蛋白表达变化。
方法
采用反向Northern印迹法检测毛果芸香碱诱导的颞叶癫痫（TLE）大鼠和年龄匹配对照的单个解离海马齿状颗粒细胞、TLE患者海马手术标本的齿状颗粒细胞以及从人类局灶性皮质发育异常标本中显微切割的发育异常神经元中EAAT3/EAAC1 mRNA的表达。用EAAT3/EAAC1抗体对大鼠和人类海马及皮质发育异常组织进行免疫标记，以证实mRNA表达分析结果。
结果
与对照大鼠的齿状颗粒细胞相比，自发癫痫大鼠的齿状颗粒细胞中EAAT3/EAAC1 mRNA表达增加了近三倍。TLE患者的人类齿状颗粒细胞中EAAT3/EAAC1 mRNA水平也很高，与死后对照组织的非发育异常神经元相比，皮质发育异常中的发育异常神经元中该水平显著升高。未观察到另一种谷氨酸转运体EAAT2/GLT-1的表达差异。免疫标记显示，TLE大鼠和人类的齿状颗粒细胞以及人类皮质发育异常组织中的发育异常神经元中EAAT3/EAAC1蛋白表达增强。
结论
癫痫大鼠和人类海马及新皮质的神经元中均存在EAAT3/EAAC1 mRNA和蛋白水平升高的情况。海马和新皮质癫痫中EAAT3/EAAC1的上调可能是细胞外谷氨酸浓度的重要调节因子，可能是这些细胞类型对反复癫痫发作的一种反应。
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