BACKGROUND Temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) is a common pharmaco-resistant epilepsy referred for adult epilepsy surgery. Though associated with prolonged febrile seizures (FS) in childhood, the neurobiological basis for this relationship is not fully understood and currently no preventive or curative therapies are available. DNA methylation, an epigenetic mechanism catalyzed by DNA methyltransferases (DNMTs), potentially plays a pivotal role in epileptogenesis associated with FS. In an attempt to start exploring this notion, the present cross-sectional pilot study investigated whether global DNA methylation levels (5-mC and 5-hmC markers) and DNMT isoforms (DNMT1, DNMT3a1, and DNMT3a2) expression would be different in hippocampal and neocortical tissues between controls and TLE patients with or without a history of FS. RESULTS We found that global DNA methylation levels and DNMT3a2 isoform expression were lower in the hippocampus for all TLE groups when compared to control patients, with a more significant decrease amongst the TLE groups with a history of FS. Interestingly, we showed that DNMT3a1 expression was severely diminished in the hippocampus of TLE patients with a history of FS in comparison with control and other TLE groups. In the neocortex, we found a higher expression of DNMT1 and DNMT3a1 as well as increased levels of global DNA methylation for all TLE patients compared to controls. CONCLUSION Together, the findings of this descriptive cross-sectional pilot study demonstrated brain region-specific changes in DNMT1 and DNMT3a isoform expression as well as global DNA methylation levels in human TLE with or without a history of FS. They highlighted a specific implication of DNMT3a isoforms in TLE after FS. Therefore, longitudinal studies that aim at targeting DNMT3a isoforms to evaluate the potential causal relationship between FS and TLE or treatment of FS-induced epileptogenesis seem warranted.

中文翻译：

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DNA甲基转移酶同工型在有高热惊厥史的癫痫患者的颞叶中表达。

背景技术伴有海马硬化（HS）的颞叶癫痫（TLE）是成人癫痫手术中常见的对药物具有抗药性的癫痫。尽管与儿童期高热性惊厥（FS）有关，但这种关系的神经生物学基础尚不完全清楚，目前尚无预防或治疗方法。DNA甲基化是DNA甲基转移酶（DNMT）催化的表观遗传机制，在与FS相关的癫痫发生中可能起关键作用。为了尝试探索这一概念，本断层先导研究调查了海马和海马中的总体DNA甲基化水平（5-mC和5-hmC标记）和DNMT亚型（DNMT1，DNMT3a1和DNMT3a2）表达是否会有所不同。对照和TLE患者之间有或没有FS史的新皮层组织。结果我们发现，与对照组相比，所有TLE组的海马体中总体DNA甲基化水平和DNMT3a2亚型表达均较低，在有FS史的TLE组中，其下降幅度更大。有趣的是，我们显示，与对照组和其他TLE组相比，具有FS病史的TLE患者的海马中DNMT3a1表达严重降低。在新皮层中，我们发现与对照组相比，所有TLE患者的DNMT1和DNMT3a1的表达更高，并且全局DNA甲基化水平提高。结论总之，该描述性横断面试验研究的结果表明，DNTLE1和DNMT3a同工型表达的大脑区域特定变化，以及有或没有FS史的人TLE中的整体DNA甲基化水平。他们强调了FS后TLE中DNMT3a亚型的特殊含义。因此，有必要进行针对DNMT3a同工型的纵向研究，以评估FS和TLE之间的潜在因果关系或FS诱导的癫痫发生的治疗。