Retrospective studies suggest that precipitating events such as prolonged seizures, stroke, or head trauma increase the risk of developing epilepsy later in life. The process of epilepsy development, known as epileptogenesis, is associated with changes in the expression of a myriad of genes. One of the major challenges for the epilepsy research community has been to determine which of these changes contributes to epileptogenesis, which may be compensatory, and which may be noncontributory. Establishing this for any given gene is essential if it is to be considered a therapeutic target for the prevention or treatment of epilepsy. Our laboratories have examined alterations in gene expression related to inhibitory neurotransmission that have been proposed as contributing factors in epileptogenesis. The GABA_A receptor mediates most fast synaptic inhibition, and changes in GABA_A receptor subunit expression and function have been reported in adult animals beginning immediately after prolonged seizures (status epilepticus [SE]) and continue as animals become chronically epileptic. Prevention of GABA_A receptor subunit changes after SE using viral gene transfer inhibits development of epilepsy in an animal model, suggesting that these changes directly contribute to epileptogenesis. The mechanisms that regulate differential expression of GABA_A receptor subunits in hippocampus after SE have recently been identified, and include the CREB-ICER, JAK-STAT, BDNF, and Egr3 signaling pathways. Targeting signaling pathways that alter the expression of genes involved in epileptogenesis may provide novel therapeutic approaches for preventing or inhibiting the development of epilepsy after a precipitating insult.

中文翻译：

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癫痫发生基因的改变。

回顾性研究表明，长期癫痫发作、中风或头部外伤等突发事件会增加晚年患癫痫的风险。癫痫发展的过程，称为癫痫发生，与无数基因表达的变化有关。癫痫研究界面临的主要挑战之一是确定这些变化中哪些会导致癫痫发生，哪些可能是补偿性的，哪些可能是非贡献性的。如果要将任何给定基因视为预防或治疗癫痫的治疗靶点，就必须为任何给定基因建立这一点。我们的实验室研究了与抑制性神经传递相关的基因表达变化，这些变化被认为是癫痫发生的促成因素。GABA _A受体介导最快速的突触抑制，据报道，成年动物在长期癫痫发作（癫痫持续状态 [SE]）后立即开始发生 GABA _A受体亚基表达和功能的变化，并随着动物变得慢性癫痫而持续。使用病毒基因转移预防SE 后GABA _A受体亚基变化可抑制动物模型中癫痫的发展，这表明这些变化直接促进了癫痫的发生。调控 GABA _A差异表达的机制最近鉴定了 SE 后海马中的受体亚基，包括 CREB-ICER、JAK-STAT、BDNF 和 Egr3 信号通路。靶向改变参与癫痫发生的基因表达的信号通路可能提供新的治疗方法，用于预防或抑制诱发性损伤后癫痫的发展。