热惊厥增加癫痫易感性的遗传机制研究

Neuroplasticity plays an important role in epileptogenesis and epilepsy is currently considered to be the development of abnormal neural networks induced by risk factors. Early development period is crucial for the formation of neural networks. Thus the event happened during early developmental period may play a very important role in the formation of epileptic networks. Recently, it has been demonstrated that exposing young animals to an enriched environment enhances the abilities related to neuroplasticity in their future offspring, even if the offspring are not exposed to enriched environment, suggesting the acquired enhancement of plasticity can transmitted to the offspring. However, it is still unknown whether acquired enhancement of susceptibility to epilepsy transmit to the offspring or not. Complex febrile seizures (FSs) are common during early developmental period, and it has intensive relationship with epilepsy. Our preliminary experiment showed that the enhanced susceptibility of seizures after acquired FSs can transmitted to their offspring in MES seizures models; (2) the transgenerational transmission showed severity-dependent characteristics; (3) the transgenerational transmission was through the mother. These results dramatically expanded previous finding that acquired FSs enhances the susceptibility of seizures, by showing that it also enhances susceptibility of seizures in their future offspring, even if the offspring do not experienced FSs. Therefore, in this program, using acquired FSs model, combining with several classic models of epilepsy, we will further demonstrated the effect of FSs on epileptic susceptibility, the characteristics of transmission and mechanism of transmission. Our study will promote the understanding of the epileptogenesis.

癫痫是致病因素作用于高度可塑的大脑，形成异常神经网络的结果。婴幼儿时期被认为是神经网络形成的关键时期之一。最近研究报道，婴幼儿时期通过经历复杂环境所获得的与神经可塑性密切相关的能力可以遗传，提示后天形成的神经网络改变可以遗传。然而，目前国际上尚无婴幼儿时期的关键事件引起癫痫易感性增加可以遗传的报道。复杂热惊厥(complex febrile seizures, FSs)在临床上被认为是婴幼儿时期发生的与其后癫痫形成密切相关的事件。课题组的预实验发现，幼年时经过FSs引起大鼠的对癫痫最大电休克模型的易感性增加可以遗传，这种遗传与FSs的发作强度密切相关，而且还显示了母系遗传特性。因此，本课题拟利用获得性FSs模型，结合多个癫痫模型，进一步明确FSs对癫痫易感性的作用，探讨热惊厥增加癫痫易感性的遗传特点，并试图阐明癫痫形成过程中有别于传统观点的遗传机制。本课题的完成会推动对癫痫发病机制的理解。

癫痫是致病因素作用于高度可塑的大脑，形成异常神经网络的结果。婴幼儿时期被认为是神经网络形成的关键时期之一。最近研究报道，婴幼儿时期通过经历复杂环境所获得的与神经可塑性密切相关的能力可以遗传，提示后天形成的神经网络改变可以遗传。然而，目前国际上尚无婴幼儿时期的关键事件引起癫痫易感性增加可以遗传的报道。复杂热惊厥(complex febrile seizures, FSs)在临床上被认为是婴幼儿时期发生的与其后癫痫形成密切相关的事件。课题组发现，幼年时经过FSs引起大鼠的对癫痫最大电休克模型的易感性增加可以遗传，这种遗传与FSs的发作强度密切相关，而且还显示了母系遗传特性。因此，本课题拟利用获得性FSs模型，结合多个癫痫模型，进一步明确FSs对癫痫易感性的作用，探讨热惊厥增加癫痫易感性的遗传特点，并试图阐明癫痫形成过程中有别于传统观点的遗传机制。本课题推动对癫痫发病机制的理解。