Expression analysis of metabotropic glutamate receptors I and III in mouse strains with different susceptibility to experimental temporal lobe epilepsy
Expression analysis of metabotropic glutamate receptors I and III in mouse strains with different susceptibility to experimental temporal lobe epilepsy
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DOI：
10.1016/j.neulet.2004.11.008
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发表时间：
2005-03-03
影响因子：
2.5
通讯作者：
Becker, AJ
中科院分区：
文献类型：
--
作者：
Chen, J;Larionov, S;Becker, AJ
海马区兴奋性增强是耐药人类颞叶癫痫(TLE)的致病标志。代谢型谷氨酸受体(MGluRs)根据序列同源性、信号转导机制和药理特性可分为三类。一般来说，I类mGluRs介导神经元兴奋，而II类和III类mGluRs激活则减少突触传递。在人类TLE中已经描述了I类和III类mGluR亚基表达的变化。MGluR表达的改变是否与癫痫易感性或海马区损伤的差异有关仍有待确定。在这里，我们检测了实验性TLE中I类mGluRs(mGluR1和5)和III类mGluR(mGluR4和7)的转录水平，并将mGluR亚基的差异表达与匹罗卡品诱导的TLE小鼠品系依赖的易感性相关联。通过实时荧光RT-PCR检测了CD1、C57BL/6和FVB/N小鼠癫痫齿状回颗粒细胞(DG)中mGluRs 1、4、5和7的表达。与C57BL/6和CD1品系相比，FVB/N小鼠似乎更容易受到匹罗卡品诱导的癫痫发作的影响。RT-PCR分析显示，癫痫CD1小鼠的抑制性mGluR4表达增加，兴奋性mGluR1表达下调，C57BL/6的兴奋性mGluR1和5表达减少(p<；0.05，n=6)，而FVB/N株的兴奋性mGluR1和兴奋性mGluR5表达减少。这些结果表明兴奋性mGluR1和抑制类mGluR III的差异表达与癫痫敏感性和海马区损伤有关。我们的数据表明，mGluRs I类和III类是干扰海马区癫痫发生和过度兴奋的有趣的潜在治疗靶点。(C)2004爱思唯尔爱尔兰有限公司。保留所有权利。
Increased hippocampal excitability constitutes a pathogenetic hallmark of pharmacoresistant human temporal lobe epilepsy (TLE). Metabotropic glutamate receptors (mGluRs) can be subdivided into three classes based on sequence homologies, mechanisms of signal transduction as well as pharmacological characteristics. Generally, class I mGluRs mediate neuronal excitation whereas activation of class II and III mGluRs decreases synaptic transmission. Changes in expression of class I and III mGluR subunits have been described in human TLE. It remains to be determined whether altered mGluR expression relates to differences in seizure susceptibility or hippocampal damage. Here, we examine the transcription levels of mGluRs class I (mGluR1 and 5) and III (mGluR4 and 7) in experimental TLE and correlate differential mGluR subunit expression with mouse-strain-dependent susceptibility to TLE induced by pilocarpine.Expression of mGluRs 1, 4, 5 and 7 was determined in epileptic dentate gyrus granule cells (DG) in CD1, C57BL/6 and FVB/N mice by real time RT-PCR. FVB/N mice appear significantly more vulnerable to pilocarpine-induced seizures than C57BL/6 and CD1 strains. RT-PCR analysis demonstrates an increased expression of inhibitory mGluR 4 and downregulation of excitatory mGluR1 in epileptic CD1 mice and a decrease of the excitatory mGluRs 1 and 5 in C57BL/6 (p < 0.05, n = 6 each) but not in the FVB/N strain.These results correlate differential expression of excitatory class mGluR1 and inhibitory class mGluR III to seizure susceptibility and hippocampal damage. Our data suggest mGluRs class I and III as interesting potential therapeutic targets to interfere with hippocampal epileptogenesis and hyperexcitability. (C) 2004 Elsevier Ireland Ltd. All rights reserved.