Alterations in methylome in three experimental models of epilepsy-differences and similarities

• Autorzy: Lukasiuk K.
• Języki publikacji: EN

Abstrakty

EN

According to the WHO, 60 million people in the world have epilepsy, and in 30% of patients are drug resistant. Finding new mechanisms involved in development of epilepsy that could be a targets for new therapies is an unmet medical need. Recent evidence points to epigenetic mechanisms which occur during epileptogenesis, including acute changes in DNA methylation, histone modifications, and microRNA expression which have been reported in different epilepsy models and in human tissue. In our work we tested the hypothesis that epileptogenesis is accompanied by specific changes in DNA methylation that are common for different epilepsies regardless of etiology. Using Methyl-capture and massive parallel sequencing (Methyl-Seq), we compared alterations in genomic DNA methylation in the hippocampal CA1/CA3 fields at 3 months following epileptogenic injury in three experimental models of epilepsy: focal amygdala stimulation, systemic pilocarpine injection, or lateral fluid-percussion induced TBI in rats. We have found that in all three injury models methylation status differentiates controls from injured animals. All three models are characterized by markedly increased methylation in gene bodies and by hypomethylation in non-genic areas. However, analysis of the precise locations of methylation events in the genome did not identify any regions with altered methylation which had been common to all three models, and only a few regions common to any two models. We found only modest association of altered methylation and gene expression. Changes in methylation status occur in experimental models of epilepsy, however the methylation pattern is dependent on etiology and can underlie model specific mechanisms or stage of epileptogenesis.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S17-S18

Twórcy

autor

Lukasiuk K.

• Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland