Parallel changes in the promoter methylation of voltage-gated T-type calcium channel alpha 1 subunit G and histone deacetylase activity in the WAG/Rij model of absence epilepsy

Abstract

Objective: In the last two decades, research on epigenetic mechanisms has expanded dramatically. Recent studies demonstrated that epigenetic mechanisms regulate epilepsy and epileptogenic pathologies. In this study, we aimed to investigate changes in the promoter methylation status of the voltage-gated T-type calcium channel alpha 1 subunit G (CACNA1G) gene and total histone deacetylase activity in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats which is one of the commonly used genetic absence rat models of epilepsy in the three different age groups (3, 6, and 9 months old) on both sexes. 
 Material and Method: Evaluation of changes in the spike-wave discharges (SWDs) was performed with electrocorticography (ECoG). The promoter methylation status of the CACNA1G gene was determined by methylation-specific PCR (MSP), and histone deacetylase (HDAC) activity was determined spectrophotometrically. 
 Results: Our results demonstrated that the number of SWDs increased time-dependent in WAG/Rij. Additionally, it was observed that CACNA1G promoter methylation decreased, and total HDAC activity increased with age in both sexes. 
 Conclusion: Our results provide further support for epigenetic regulation in the absence epilepsy phenotype and suggest that the underlying mechanism behind the increase in the number of SWDs with age in the WAG/Rij animals might be regulated by CACNA1G promoter methylation or HDAC activity.