Epigenetic changes induced by adenosine augmentation therapy prevent epileptogenesis.

ABSTRACT: Epigenetic modifications, including changes in DNA methylation, lead to altered gene expression and thus may underlie epileptogenesis via induction of permanent changes in neuronal excitability. Therapies that could inhibit or reverse these changes may be highly effective in halting disease progression. Here we identify an epigenetic function of the brain's endogenous anticonvulsant adenosine, showing that this compound induces hypomethylation of DNA via biochemical interference with the transmethylation pathway. We show that inhibition of DNA methylation inhibited epileptogenesis in multiple seizure models. Using a rat model of temporal lobe epilepsy, we identified an increase in hippocampal DNA methylation, which correlates with increased DNA methyltransferase activity, disruption of ade

SUBMITTER: Williams-Karnesky RL 

PROVIDER: S-EPMC3726154 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature