Ccny knockout mice display an enhanced susceptibility to kainic acid-induced epilepsy

Hongik Hwang, Jiyeon Seo, Yuri Choi, Eunsil Cho, Heesung Sohn, Jaewon Jang, A. Ram Lee, Jiyoung Lee, Suyeon Kim, Hae Young Koh, Mikyoung Park

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Cyclin Y (CCNY) is a member of cyclin superfamily proteins involved in the regulation of the cell cycle in proliferating cells. Intriguingly, CCNY is highly expressed in terminally differentiated neuronal cells of multiple brain regions and acts as a postsynaptic protein, which plays an inhibitory role in long-term potentiation. However, the pathophysiological significance of CCNY in the nervous system remains largely unexplored. In this study, we revisited our RNA-sequencing (RNA-seq) data obtained from cultured hippocampal neurons virally overexpressing or depleting CCNY. Using RNA-seq-based bioinformatic disease analysis and synaptic gene ontology analysis, we identified that numerous genes associated with epilepsy (e.g. Chrna4, Gabrd, Nhlrc1, Reln, Samd12, Slc6a1, etc.) or neurodegenerative diseases (e.g. Psen1, Pdyn, Ndrg1, etc.) are affected by the level of CCNY expression. In agreement with the RNA-seq-based disease analysis, we found that Ccny knockout (KO) mice are more susceptible to kainic acid-induced epilepsy than wild-type mice. In addition, some epilepsy-associated genes that are regulated by CCNY levels were further validated in the brain of Ccny KO mice at the mRNA and protein levels. Collectively, our findings indicate that CCNY shifts the expression profile of epilepsy-associated genes and exerts a protective effect against kainic acid-induced epilepsy, suggesting CCNY as a potential pharmaceutical candidate for the treatment of epilepsy.

Original languageEnglish
Article number105100
JournalPharmacological Research
Volume160
DOIs
StatePublished - Oct 2020

Keywords

  • Cyclin Y
  • Disease analysis
  • Epilepsy
  • RNA-sequencing
  • Seizures
  • Synaptic gene ontology
  • Transcriptome

Fingerprint

Dive into the research topics of 'Ccny knockout mice display an enhanced susceptibility to kainic acid-induced epilepsy'. Together they form a unique fingerprint.

Cite this