DNA甲基化在大鼠复杂性热惊厥后引起的记忆损伤及其传代中的作用研究

Complex febrile seizures (FSs) are common diseases during early developmental period, and it closely related with memory defects. However, it is still unknown whether acquired memory defects can transmit to the offspring. Our preliminary experiment showed that the memory defects after acquired FSs can transmitted to their offspring in inhibitory avoidance task and contextual fear memory task, the transgenerational transmission may not related with maternal abuse. Moreover, it is reported that epigenetics modification may participate in memory formation and transgenerational transmission, our preliminary experiment showed that DNA transmethylases increased in FSs rats and their offspring. Therefore, in this program, using internationally accepted acquired FSs model, combining with several memory models, we will demonstrated the effect of FSs on memory and the characteristics of transmission, and preliminary clarify the underlying mechanism. Our study will promote the understanding of the mechanisms of transgenerational transmission of memory defects after FSs.

复杂性热惊厥(complex febrile seizures, FSs)在临床上被认为是婴幼儿时期的常见疾病，并且可以引起成年后的记忆损伤，但尚不清楚其是否能够遗传至下一代。申请人的预实验发现，幼年时经历过FSs的大鼠在被动回避反应以及恐惧反应实验中表现出明显的记忆损伤，而且这种损伤能够遗传给未经历过复杂性热惊厥发作的子代，并且这种遗传与热惊厥母鼠可能的异常抚育行为无关。预实验初步结果还发现DNA甲基转移酶在FSs大鼠及其子代中明显增加，同时在复杂热惊厥后给予DNA甲基转移酶抑制剂能够抑制成年后的记忆损伤，提示幼年时FSs引起了DNA甲基化程度的改变，进一步启发我们可以通过早期干预的手段来防治热惊厥病人以及下一代的认知行为障碍。因此，本课题拟通过国际公认的FSs模型结合多种记忆模型，利用基因测序，病毒干预以及电生理等手段，深入研究FSs后记忆损伤传代的遗传特点以及DNA甲基化的参与机制。