Gene expression profiling of a hypoxic seizure model of epileptogenesis in the rat.

Gene expression in the control samples was found to be consistent with known processes of neuronal maturation in the rat for the given time window. The hypoxic seizure response was found to be saliently enriched for components of the PI3K/mTOR and Wnt signaling pathways, alongside gene sets representative of glutamatergic, synaptic and axonal processes, perhaps regulated as a downstream consequence of activation of these pathways. Wnt signaling components were also found enriched in the more specifically epileptogenic NBQX-responsive gene set. While activation of the mTOR pathway is consistent with its known role in epileptogenesis and strengthens the case for mTOR or PI3K pathway inhibitors as potential anti-epileptogenic drugs, investigation of the role of Wnt signaling and the effect of cognate inhibitors offers a parallel avenue of research toward anti-epileptogenic treatment.本研究发现，在指定时间窗内，对照样本的基因表达与已报道的大鼠神经元成熟过程相符。缺氧性癫痫发作响应显著富集PI3K/mTOR（磷脂酰肌醇3-激酶/哺乳动物雷帕霉素靶蛋白）与Wnt信号通路的相关组分，同时包含代表谷氨酸能、突触及轴突过程的特征基因集，此类基因集或为上述通路激活的下游调控产物。在更具致痫特异性的NBQX响应基因集中，同样检测到Wnt信号通路组分的富集。尽管mTOR通路的激活与其已知的致痫作用一致，且进一步支持了mTOR或PI3K通路抑制剂作为潜在抗致痫药物的可行性，但针对Wnt信号通路的作用及其同源抑制剂的效果开展研究，可为抗致痫治疗提供全新的平行研究方向。