Molecular regulation of brain metabolism underlying circadian epilepsy

Felix Chan, Judy Liu

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)S32-S38
Issue numberSuppl.1
Early online date4 Jan 2021
Publication statusPublished - Feb 2021

Bibliographical note

© 2021 International League Against Epilepsy. This is the peer reviewed version of the following article: Chan, F, Liu, J. Molecular regulation of brain metabolism underlying circadian epilepsy. Epilepsia. 2021; 62(Suppl. 1): S32– S48, which has been published in final form at: This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.


  • circadian
  • clock genes
  • epigenetic
  • Epilepsy
  • metabolism


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