Affiliation:
1. Center for Circadian Clocks, Soochow University, Suzhou 215123, China
2. School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou 215123, China
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.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
Priority Academic Program Development of Jiangsu Higher Education Institutions
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis