Transcriptome of the Wistar audiogenic rat (WAR) strain following audiogenic seizures

The Wistar Audiogenic Rat (WAR) is a model whose rats are predisposed to develop seizures following acoustic stimulation. We aimed to establish the transcriptional profile of the WAR model, searching for genes that help in understanding the molecular mechanisms involved in the predisposition and seizures expression of this strain. RNA-Seq of the corpora quadrigemina of WAR and Wistar rats subjected to acoustic stimulation revealed 64 genes differentially regulated in WAR. We validated twelve of these genes by qPCR in stimulated and naive (nonstimulated) WAR and Wistar rats. Among these, Acsm3 was upregulated in WAR in comparison with both control groups. In contrast, Gpr126 and Rtel1 were downregulated in naive and stimulated WAR rats in comparison with the Wistar controls. Qdpr was upregulated only in stimulated WAR rats that exhibited audiogenic seizures. Our data show that there are genes with differential intrinsic regulation in the WAR model and that seizures can alter gene regulation. We identified new genes that might be involved in the epileptic phenotype and comorbidities of the WAR model.维斯塔耳源性大鼠（Wistar Audiogenic Rat，下称WAR）是一类大鼠模型，其个体易在声学刺激后引发癫痫发作。本研究旨在构建WAR模型的转录组图谱，以期发掘可用于解析该品系大鼠易感性及癫痫发作表现分子机制的相关基因。对接受声学刺激的WAR及普通Wistar大鼠的四叠体进行RNA测序（RNA-Seq）后，共筛选得到64个在WAR大鼠中存在差异表达的基因。本研究通过实时定量聚合酶链反应（quantitative real-time PCR，下称qPCR），在受刺激与未受刺激（非刺激状态）的WAR及Wistar大鼠中验证了其中12个基因的表达差异。其中，相较于两个对照组，Acsm3在WAR大鼠中呈上调表达；与之相反，Gpr126与Rtel1在未受刺激及受刺激的WAR大鼠中，相较于Wistar对照组均呈下调表达；Qdpr仅在出现耳源性癫痫发作的受刺激WAR大鼠中呈上调表达。本研究数据表明，WAR模型中存在固有表达差异的基因，且癫痫发作可改变基因表达调控模式。本研究还发掘出可能与WAR模型的癫痫表型及共病症状相关的新基因。