Reprogramming the Circadian Dynamics of Epileptic Genes in Mouse Temporal Lobe Epilepsy

Abstract

Temporal lobe epilepsy (TLE) is a common and severe epilepsy displaying rhythmicity in humans and animals. However, how the circadian clock contributes to TLE remains elusive. A recent circadian analysis of the ventral hippocampal transcriptome of pilocarpine-induced TLE mice revealed as many as 1650 rhythmically expressed transcripts. Here, a comparison of the mouse ventral hippocampal transcriptome with the human epilepsy-related gene set identified 315 possible mouse epilepsy-related genes. Rhythmicity analysis classified them into arrhythmicity, loss-of-rhythmicity, gain-of-rhythmicity, and rhythmicity-maintaining groups. KEGG and GO analyses of these mouse epilepsy genes suggest their involvement in circadian entrainment. In TLE mice, Htr1d, Drd2, and Chrna3 lose rhythmicity, but P2rx7 gains rhythmicity; the up-regulation of Htr1d and Drd2 and down-regulation of Chrna3 inhibit adenylate cyclase (AC), and up-regulation of Htr1d, Drd2, and P2rx7 activates protein kinase C (PKC). Together, these results suggest that epilepsy can disrupt the circadian dynamics of the epileptic genes, shed light on possible TLE pathogenesis, and provide potential targets for TLE diagnosis and chronotherapy.

Circadian dynamics of the Zbtb14 protein in the ventral hippocampus are disrupted in epileptic mice

“…Although epileptic seizures appear as random events, clinical data, patient journals, and basic research have shown that seizures occur more often at certain times over the circadian cycle (Hofstra et al, 2009; Karoly et al, 2021; Sun and Wang, 2023; Zhang et al, 2021). The investigation of cycles from circadian to circannual is becoming an important research topic due to the prospect of chronotherapy – the administration of drugs when they are most effective.…”