Differential changes in mGlu2 and mGlu3 gene expression following pilocarpine-induced status epilepticus:: A comparative real-time PCR analysis
Differential changes in mGlu2 and mGlu3 gene expression following pilocarpine-induced status epilepticus:: A comparative real-time PCR analysis
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DOI：
10.1016/j.brainres.2008.05.073
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发表时间：
2008-08-21
期刊：
影响因子：
2.9
通讯作者：
Garrido-Sanabria, Emilio R.
中科院分区：
文献类型：
--
作者：
Ermolinsky, Boris;Otalora, Luis F. Pacheco;Garrido-Sanabria, Emilio R.
II组代谢型谷氨酸（mGlu 11）受体亚型2和3（mGlu 2和mGlu 3）是海马神经元兴奋性和突触可塑性的微妙调节剂。近年来，研究人员研究了作用于mGlu 11受体的化合物的潜在神经保护和抗惊厥作用。然而，mGlu 2和mGlu 3的异常表达和功能在颞叶癫痫中已有报道，这种现象可能限制这些潜在的新抗癫痫药物的治疗效果。在这里，我们研究了毛果芸香碱诱导的癫痫持续状态（SE）和随后的癫痫发生后mGlu 2和mGlu 3 mRNA的变化。通过delta-delta CT方法的定量实时PCR（qrtPCR）比较分析评估基因表达的相对变化。在SE后不同时间（24 h、10 d、1个月和2个月以上）处死毛果芸香碱治疗组和对照组大鼠。从显微解剖的齿状回中分离总RNA，并使用甘油醛-3-磷酸脱氢酶（GAPDH）作为内源性对照基因进行RT-PCR和qrtPCR处理。mGlu 2和mGlu 3 mRNA表达的相对定量（RQ）比分析显示，在SE后24 h，两个靶点均显著下调。SE后10天基因表达部分恢复，SE后1个月达到对照水平。SE后2个月，mGlu 2 mRNA表达显著下调至对照表达的41%，而mGlu 3 mRNA与对照水平相当。我们的数据表明，mGlu 2和mGlu 3表达动态下调或选择性增强癫痫发生的关键时期。癫痫发作诱导的mGlu 2和mGlu 3受体的差异失调可能会影响这些分子靶标在癫痫治疗化合物中的可用性。(C)2008 Elsevier B. V.保留所有权利。
Group II metabotropic glutamate (mGlu 11) receptors subtype 2 and 3 (mGlu2 and mGlu3) are subtle regulators of neuronal excitability and synaptic plasticity in the hippocampus. In recent years, researchers have investigated the potential neuroprotective and anticonvulsant effects of compounds acting on mGlu 11 receptors. However, abnormal expression and function of mGlu2 and mGlu3 have been reported in temporal lobe epilepsy, a phenomena that may limit the therapeutic effectiveness of these potentially new antiepileptic drugs. Here, we investigated seizure-induced changes in mGlu2 and mGlu3 mRNA following pilocarpine-inducted status epilepticus (SE) and subsequent epileptogenesis. Relative changes in gene expression were assessed by comparative analysis of quantitative real-time PCR (qrtPCR) by the delta-delta CT method. Pilocarpine-treated and control rats were sacrificed at different periods (24 h, 10 days, one month and more than two months) following SE. Total RNA was isolated from microdissected dentate gyrus and processed for RT-PCR and qrtPCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an endogenous control gene. Analysis of relative quantification (RQ) ratios of mGlu2 and mGlu3 mRNA expression revealed a significant down-regulation of both targets at 24 h after SE. Gene expression partially recovered at 10 days following SE reaching control levels at one month after SE. Two month after SE, mGlu2 mRNA expression was significantly down-regulated to similar to 41% of control expression whereas mGlu3 mRNA was comparable to control levels. Our data indicate that mGlu2 and mGlu3 expression is dynamically down-regulated or selectively enhanced during critical periods of epileptogenesis. Seizure-induced differential dysregulation of mGlu2 and mGlu3 receptors may affect the availability of these molecular targets for therapeutic compounds in epilepsy. (C) 2008 Elsevier B.V. All rights reserved.