Molecular regulation of glutamate and GABA transporter proteins by clobazam during epileptogenesis in Fe+++-induced epileptic rats
Molecular regulation of glutamate and GABA transporter proteins by clobazam during epileptogenesis in Fe+++-induced epileptic rats
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DOI：
10.1016/j.molbrainres.2005.09.010
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发表时间：
2005-12-14
期刊：
影响因子：
--
通讯作者：
Willmore, LJ
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文献类型：
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作者：
Doi, T;Ueda, Y;Willmore, LJ
为了评估抗癫痫药物氯巴扎姆(CLB，1，5-苯二氮卓)的分子效应，我们在杏仁核注射FeCl3诱导的慢性自发性癫痫发作大鼠上进行了一系列实验。实验动物给予CLB治疗14天。然后，我们测量了谷氨酸和GABA转运蛋白的表达，并使用实验动物和对照动物评估了这些蛋白发生的变化。CLB治疗与接受杏仁核FeCl3和CLB治疗的动物对侧海马区GLT-1的产生增加有关。CLB治疗上调慢性反复发作动物对侧海马区GABA转运体GAT3的表达。而CLB对对照组大鼠海马区或皮质中EAAC1和GAT I的表达无明显影响。慢性癫痫的发生可能与胶质兴奋性氨基酸转运体GLAST和GLT-1的产生下调有关，这两种蛋白导致细胞外谷氨酸基础浓度的增加。在兴奋期，GABA转运体的高表达导致GABA向细胞外间隙的反向转运增加。除了变构激活GABA(A)受体外，本研究提示CLB可能通过增加慢性癫痫大鼠海马区GLT-1和GAT3的表达而发挥抗癫痫作用。(C)2005 Elsevier B.V.保留所有权利。
To assess the molecular effects of the antiepileptic drug clobazam (CLB, 1,5-benzodiazepine), a benzodiazepine effective in the management of epilepsy, we performed a series of experiments using rats with chronic, spontaneous recurrent seizures induced by amygdalar injection of FeCl3. Experimental animals were treated for 14 days with CLB. We then measured the expression of glutamate and GABA transporter proteins and evaluated the changes that occurred in these proteins using both experimental and control animals. CLB treatment was associated with an increase in the production of GLT-1 in the contra-lateral hippocampus of animals receiving amygdalar FeCl3 and CLB treatment. CLB treatment up-regulated the GABA transporter GAT3 in the contra-lateral hippocampus of animals with chronic, recurrent seizures. In contrast, CLB had no effect on the expression of EAAC1 and GAT I in the hippocampus or the cortex in control animal groups. Chronic epileptogenesis may be associated with down-regulation of the production of glial excitatory amino acid transporters, GLAST and GLT-1, proteins that cause increase in the basal extracellular concentrations of glutamate. Elevated GABA transporter expression results in increased reverse transport of GABA to the extracellular space during periods of excitation. In addition to allosteric activation of GABA(A) receptors, this study Suggests that CLB might exhibit its antiepileptic action by increasing GLT-1 expression and GAT3 in the hippocampus of rats with chronic seizures. (c) 2005 Elsevier B.V. All rights reserved.