Epigenetics and epilepsy

Abstract

Epigenetic processes in the brain involve the transfer of information arising from short-lived cellular signals and changes in neuronal activity into lasting effects on gene expression. Key molecular mediators of epigenetics include methylation of DNA, histone modifications, and noncoding RNAs. Emerging findings in animal models and human brain tissue reveal that epilepsy and epileptogenesis are associated with changes to each of these contributors to the epigenome. Understanding and influencing the molecular mechanisms controlling epigenetic change could open new avenues for treatment. DNA methylation, particularly hypermethylation, has been found to increase within gene body regions and interference with DNA methylation in epilepsy can change gene expression profiles and influence epileptogenesis. Posttranscriptional modification of histones, including transient as well as sustained changes to phosphorylation and acetylation, have been reported, which appear to influence gene expression. Finally, roles have emerged for noncoding RNAs in brain excitability and seizure thresholds, including microRNA and long noncoding RNA. Together, research supports strong effects of epigenetics influencing gene expression in epilepsy, suggesting future therapeutic approaches to manipulate epigenetic processes to treat or prevent epilepsy.