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

Madhavi Pusalkar; Shreya Ghosh; Minal Jaggar; Basma Fatima Anwar Husain; Sanjeev Galande; Vidita A Vaidya

doi:10.1093/ijnp/pyw040

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

Int J Neuropsychopharmacol. 2016 Sep 21;19(9):pyw040. doi: 10.1093/ijnp/pyw040. Print 2016 Sep.

Authors

Madhavi Pusalkar¹, Shreya Ghosh¹, Minal Jaggar¹, Basma Fatima Anwar Husain¹, Sanjeev Galande¹, Vidita A Vaidya²

Affiliations

¹ Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India (Dr Pusalkar, Ms Ghosh, Ms Jaggar, Ms Husain, and Dr Vaidya); Centre of Excellence in Epigenetics, Indian Institute of Science Education and Research, Pune, Maharashtra, India (Dr Galande).
² Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India (Dr Pusalkar, Ms Ghosh, Ms Jaggar, Ms Husain, and Dr Vaidya); Centre of Excellence in Epigenetics, Indian Institute of Science Education and Research, Pune, Maharashtra, India (Dr Galande). [email protected].

Abstract

Background: Electroconvulsive seizure 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 electroconvulsive seizure. We hypothesized that electroconvulsive seizure may modulate the expression of epigenetic machinery, thus establishing potential alterations in the epigenetic landscape.

Methods: We examined the influence of acute and chronic electroconvulsive seizure on the gene expression of histone modifiers, namely histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone (lysine) demethylases as well as DNA modifying enzymes, including DNA methyltransferases, DNA demethylases, and methyl-CpG-binding proteins in the hippocampi of adult male Wistar rats using quantitative real time-PCR analysis. Further, we examined the influence of acute and chronic electroconvulsive seizure on global and residue-specific histone acetylation and methylation levels within the hippocampus, a brain region implicated in the cellular and behavioral effects of electroconvulsive seizure.

Results: Acute and chronic electroconvulsive seizure 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 electroconvulsive seizure.

Conclusions: Electroconvulsive seizure 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 electroconvulsive seizure.

Keywords: DNA demethylase; DNA methyltransferase; histone acetyltransferase; histone deacetylase; histone demethylase; histone methyltransferase; methyl-CpG-binding proteins.