Year: 2018
Type: review
Abstract: Epigenetics refers broadly to processes that influence medium- to long-term expression of genes through changes to the readability and accessibility of the genome to transcription. The mediators include DNA methylation, posttranslational modification of histone proteins, and noncoding RNAs. The present review focuses on recent findings showing epigenetic processes influence susceptibility to and severity of status epilepticus, while status epilepticus in turn drives changes to epigenetic marks that affect the gene expression landscape underlying epileptogenesis. Experimental status epilepticus triggers select, spatiotemporal hypo- and hypermethylation changes throughout the genome. Experimental manipulations that alter DNA methylation after status epilepticus are associated with amelioration of cognitive and hyperexcitability phenotypes. Prolonged seizures also modify chromatin compaction via acetylation and other changes to histones and their expression. Finally, short noncoding RNAs called microRNAs target networks of genes through posttranscriptional and other mechanisms and their modulation can alter status epilepticus as well as serve as potential molecular biomarkers. Long noncoding RNAs have also been targeted to influence expression of genes affecting electrophysiological functions of neurons. In summary, epigenetic processes can modulate status epilepticus, and status epilepticus imposes changes on the epigenome, which together provide novel insight into pathomechanisms, therapy, and biomarkers for status epilepticus.
Source: Epilepsia
DOI: 10.1111/epi.14502
Author: David C. Henshall
Institution: Royal College of Surgeons in Ireland
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G2809417774, Bioinformatics and predictive analytics for the identification of microRNA biomarkers of neonatal seizures, Antagomirs targeting microRNA-134 for seizure control in epilepsy, G3207356259, G3871896640, G393177772, G52547903, Molecular determinants of seizure-induced neuronal death and epileptogenesis, G5702163051, G5724314488, MicroRNA biofluid profiles as molecular diagnostics for epilepsy, G7591822437, MicroRNAs in the Pathogenesis, Treatment and Prevention of Epilepsy, G9000369985
OpenAlex ID: W2888983304