Hippocampal gene expression profiling in a rat model of posttraumatic epilepsy reveals temporal upregulation of lipid metabolism-related genes

Traumatic brain injury occasionally causes posttraumatic epilepsy. To elucidate the molecular events responsible for posttraumatic epilepsy, we established a rodent model that involved the injection of microliter quantities of FeCl3 solution into the amygdalar nuclear complex. We previously compared hippocampal gene expression profiles in the traumatic epilepsy model and normal rats at 5 days after brain injury (acute phase) and observed the role of inflammation. In this study, we focused on later stages of epileptogenesis. We compared gene expression profiles at 5, 15 (sub-chronic phase), and 30 days (chronic phase) after brain injury to identify temporal changes in molecular networks involved in epileptogenesis. A total of 81 genes was significantly (at least 2-fold) up- or downregulated over the course of disease progression. We found that genes related to lipid metabolism, namely, Apoa1, Gh, Mc4r, Oprk1, and Pdk4, were temporarily upregulated in the sub-chronic phase. Changes in lipid metabolism regulation might be related to seizure propagation during epileptogenesis. This temporal description of hippocampal gene expression profiles throughout epileptogenesis provides clues to potential markers of disease phases and new therapeutic targets.创伤性脑损伤（traumatic brain injury）偶可引发创伤后癫痫（posttraumatic epilepsy）。为阐明创伤后癫痫的潜在分子机制，本研究构建了一种啮齿动物模型：向其杏仁核复合体（amygdalar nuclear complex）注射微量三氯化铁（FeCl₃）溶液。本团队此前曾在脑损伤后第5天（急性期），对比该创伤癫痫模型大鼠与正常大鼠的海马基因表达谱（gene expression profiles），并明确了炎症反应的作用。本研究聚焦癫痫发生（epileptogenesis）的后期阶段，对比脑损伤后第5、15（亚慢性期）及第30天（慢性期）的基因表达谱，以解析癫痫发生相关分子网络的时序变化。共有81个基因在疾病进展过程中出现显著（至少2倍）的上调或下调表达。本研究发现，与脂质代谢相关的基因（即Apoa1、Gh、Mc4r、Oprk1及Pdk4）在亚慢性期中呈现暂时性上调。脂质代谢调控的异常可能与癫痫发生过程中的痫性传播相关。本研究对癫痫发生全过程中海马基因表达谱的时序分析，可为疾病分期的潜在标志物及新型治疗靶点提供研究线索。