Lukasiuk Katarzyna, Dabrowski Michal, Adach Alicja, Pitkänen Asla
The Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland.
Prog Brain Res. 2006;158:223-41. doi: 10.1016/S0079-6123(06)58011-2.
The main goal of this study was to identify common features in the molecular response to epileptogenic stimuli across different animal models of epileptogenesis. Therefore, we compared the currently available literature on the global analysis of gene expression following epileptogenic insult to search for (i) highly represented functional gene classes (GO terms) within data sets, and (ii) individual genes that appear in several data sets, and therefore, might be of particular importance for the development of epilepsy due to different etiologies. We focused on two well-described models of brain insult that induce the development of spontaneous seizures in experimental animals: status epilepticus and traumatic brain injury. Additionally, a few papers describing gene expression in rat and human epileptic tissue were included for comparison. Our analysis revealed that epileptogenic insults induce significant changes in gene expression within a subset of pre-defined GO terms, that is, in groups of functionally linked genes. We also found individual genes for which expression changed across different models of epileptogenesis. Alterations in gene expression appear time-specific and underlie a number of processes that are linked with epileptogenesis, such as cell death and survival, neuronal plasticity, or immune response. Particularly, our analysis highlighted alterations in gene expression in glial cells as well as in genes involved in the immune response, which suggests the importance of gliosis and immune reaction in epileptogenesis.
本研究的主要目标是在不同癫痫发生动物模型中,识别对致痫刺激的分子反应的共同特征。因此,我们比较了目前关于致痫损伤后基因表达全局分析的文献,以寻找:(i)数据集中高度富集的功能基因类别(基因本体论术语),以及(ii)出现在多个数据集中的单个基因,因此这些基因可能因不同病因在癫痫发展中具有特别重要的意义。我们重点关注两种已充分描述的脑损伤模型,它们可在实验动物中诱发自发性癫痫发作:癫痫持续状态和创伤性脑损伤。此外,还纳入了几篇描述大鼠和人类癫痫组织中基因表达的论文进行比较。我们的分析表明,致痫损伤在一组预定义的基因本体论术语内,即功能相关基因组中,诱导基因表达发生显著变化。我们还发现了在不同癫痫发生模型中表达发生变化的单个基因。基因表达的改变呈现出时间特异性,并且是与癫痫发生相关的许多过程的基础,如细胞死亡与存活、神经元可塑性或免疫反应。特别是,我们的分析突出了胶质细胞中基因表达的改变以及参与免疫反应的基因的改变,这表明胶质增生和免疫反应在癫痫发生中的重要性。