Extensive study has demonstrated that epilepsy occurs with greater frequency at certain times in the 24-h cycle. Although these findings implicate an overlap between the circadian rhythm and epilepsy, the molecular and cellular mechanisms underlying this circadian regulation are poorly understood. Because the 24-h rhythm is generated by the circadian molecular system, it is not surprising that this system comprised of many circadian genes is implicated in epilepsy. We summarized evidence in the literature implicating various circadian genes such as Clock, Bmal1, Per1, Rev-erb⍺, and Ror⍺ in epilepsy. In various animal models of epilepsy, the circadian oscillation and the steady-state level of these genes are disrupted. The downstream pathway of these genes involves a large number of metabolic pathways associated with epilepsy. These pathways include pyridoxal metabolism, the mammalian target of rapamycin pathway, and the regulation of redox state. We propose that disruption of these metabolic pathways could mediate the circadian regulation of epilepsy. A greater understanding of the cellular and molecular mechanism of circadian regulation of epilepsy would enable us to precisely target the circadian disruption in epilepsy for a novel therapeutic approach.

中文翻译：

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昼夜节律性癫痫脑代谢的分子调控

广泛的研究表明，癫痫在 24 小时周期中的某些时间发生的频率更高。尽管这些发现暗示了昼夜节律和癫痫之间的重叠，但人们对这种昼夜节律调节的分子和细胞机制知之甚少。因为 24 小时节律是由昼夜节律分子系统产生的，所以这个由许多昼夜节律基因组成的系统与癫痫有关也就不足为奇了。我们总结了文献中涉及多种昼夜节律基因的证据，例如 Clock、Bmal1、Per1、Rev-erb⍺ 和 Ror⍺ 在癫痫中的作用。在各种癫痫动物模型中，这些基因的昼夜节律振荡和稳态水平被破坏。这些基因的下游途径涉及大量与癫痫相关的代谢途径。这些途径包括吡哆醛代谢、雷帕霉素途径的哺乳动物靶标和氧化还原状态的调节。我们提出这些代谢途径的破坏可以介导癫痫的昼夜节律调节。对癫痫昼夜节律调节的细胞和分子机制有更深入的了解，这将使我们能够精确地针对癫痫的昼夜节律紊乱，以寻求一种新的治疗方法。