Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Neuromodulation, Beijing Municipal Science and Technology Commission, Beijing 100050, China.
Beijing Key Laboratory of Neuromodulation, Beijing Municipal Science and Technology Commission, Beijing 100050, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Neuroscience. 2019 Jan 1;396:187-199. doi: 10.1016/j.neuroscience.2018.10.021. Epub 2018 Nov 20.
The molecular mechanisms underlying the development of epilepsy, i.e., epileptogenesis, are due to altered expression of a series of genes. Global expression profiling of temporal lobe epilepsy is confounded by a number of factors, including the variability among animal species, animal models, and tissue sampling time-points. In this study, we pooled two microarray datasets of the most used pilocarpine and kainic acid epilepsy models from the Gene Expression Omnibus database. A total of 567 known and novel genes were commonly differentially expressed across the two models. Pathway analyses demonstrated that the dysregulated genes were involved in 46 pathways. Real-time PCR and western blot analysis confirmed the activation of extracellular matrix (ECM)/integrin signaling pathways. Moreover, targeting ECM/integrin signaling inhibits astrocyte activation and promotes neuron injury in the hippocampus of epileptic mice. This study may provide a "gene/pathway database" that with further investigation can determine the mechanisms underlining epileptogenesis and the possible targets for neuron protection in the hippocampus after status epilepticus.
癫痫发生的分子机制（即癫痫发生）是由于一系列基因表达的改变。颞叶癫痫的全基因组表达谱分析受到许多因素的干扰，包括动物物种、动物模型和组织采样时间点的变异性。在这项研究中，我们汇集了来自基因表达综合数据库的最常用匹罗卡品和海人酸癫痫模型的两个微阵列数据集。共有 567 个已知和新的基因在两种模型中共同差异表达。通路分析表明，失调的基因参与了 46 条通路。实时 PCR 和 Western blot 分析证实细胞外基质 (ECM)/整合素信号通路的激活。此外，靶向 ECM/整合素信号通路可抑制癫痫小鼠海马中的星形胶质细胞激活并促进神经元损伤。这项研究可能提供一个“基因/通路数据库”，通过进一步研究可以确定癫痫发生的机制以及癫痫持续状态后海马中神经元保护的可能靶点。
