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.

威斯达耳源性癫痫大鼠（Wistar Audiogenic Rat, WAR）是一类经声刺激后易诱发癫痫发作的实验动物模型。本研究旨在构建WAR模型的转录组谱，以筛选有助于解析该品系大鼠癫痫易感性及发作表现相关分子机制的基因。对经声刺激的WAR大鼠及普通Wistar大鼠的中脑四叠体（corpora quadrigemina）进行RNA测序（RNA-Seq），结果显示WAR大鼠存在64个差异表达基因。本研究通过实时荧光定量PCR（quantitative real-time PCR, qPCR）对经声刺激及未受刺激的WAR与Wistar大鼠的其中12个差异基因进行了验证。其中，Acsm3在WAR大鼠中相较于两个对照组均呈上调表达；与之相反，Gpr126与Rtel1在未受刺激及经声刺激的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经声刺激WAR大鼠中呈上调表达。本研究数据表明，WAR模型中存在固有调控差异的基因，且癫痫发作可改变基因表达调控模式。本研究筛选出了可能与WAR模型的癫痫表型及共患病相关的新型基因。