Acute and Chronic Electroconvulsive Seizures (ECS) Differentially Regulate the Expression of Epigenetic Machinery in the Adult Rat Hippocampus

Abstract

Background Electroconvulsive seizure (ECS) treatment is a fast-acting antidepressant therapy that evokes rapid transcriptional, neurogenic and behavioral changes. Epigenetic mechanisms contribute to altered gene regulation, which underlies the neurogenic and behavioral effects of ECS. We hypothesized that ECS may modulate the expression of epigenetic machinery, thus establishing potential alterations in the epigenetic landscape. Methods We examined the influence of acute and chronic ECS on the gene expression of histone modifiers, namely histone acetyltransferases (HATs), histone deacetylases (HDACs), histone methyltransferases (HMTs) and histone (lysine) demethylases (KDMs), as well as DNA modifying enzymes, including DNA methyltransferases (DNMTs), DNA demethylases and methyl-CpG-binding proteins in the hippocampi of adult male Wistar rats using quantitative RT-PCR analysis. Further, we examined the influence of acute and chronic ECS on global and residue-specific histone acetylation and methylation levels within the hippocampus, a brain region implicated in the cellular and behavioral effects of ECS. Results Acute and chronic ECS induced a primarily unique, and in certain cases bidirectional, regulation of histone and DNA modifiers, and methyl-CpG-binding proteins, with an overlapping pattern of gene regulation restricted to Sirt4, Mll3, Jmjd3, Gadd45b, Tet2 and Tet3. Global histone acetylation and methylation levels were predominantly unchanged, with the exception of a significant decline in H3K9 acetylation in the hippocampus following chronic ECS. Conclusions ECS treatment evokes the transcriptional regulation of several histone and DNA modifiers, and methyl-CpG-binding proteins within the hippocampus, with a predominantly distinct pattern of regulation induced by acute and chronic ECS.