Commonalities in gene expression and methylation changes across two rat models of acquired epilepsy [RRBS]
Epileptogenesis, the process by which a normal brain develops epilepsy, is characterized by complex changes in DNA methylation and gene expression. In this study, RNA sequencing and reduced-representation bisulfite sequencing were utilized to investigate these molecular alterations in two distinct and widely used rat models of temporal lobe epilepsy: intrahippocampal electrical kindling and systemic kainic acid. These models, involving rats, differ significantly in their underlying mechanisms and histopathological outcomes, providing a unique opportunity to identify both shared and model-specific changes during epileptogenesis. By comparing these models, we uncovered common pathways that may reflect generalizable, model-independent mechanisms of epileptogenesis, alongside distinct changes that highlight the diverse molecular landscapes of each model. This integrative, multi-omics approach not only enhances our understanding of the molecular drivers of epileptogenesis but also underscores the importance of cross-model comparisons for uncovering robust and potentially therapeutic targets in epilepsy research. This dataset serves as a valuable resource for exploring the epigenomic and transcriptomic underpinnings of epilepsy. Overall design: Adult male Sprague–Dawley rats (~170–280 g) were used to investigate molecular alterations during epileptogenesis in two distinct models of temporal lobe epilepsy: systemic kainic acid and intrahippocampal electrical kindling. Animals were housed under a 12:12 light/dark cycle with ad libitum access to food and water. In the systemic kainic acid model, rats underwent electrode implantation surgery, followed by incremental kainic acid injections to induce status epilepticus. In the intrahippocampal kindling model, rats were instrumented with hippocampal electrodes and subjected to twice-daily stimulations until fully kindled. Whole hippocampi were surgically dissected 24 hours after the last seizure, flash-frozen in liquid N2, and stored at -80°C. Total RNA and DNA were extracted from left hippocampal samples using Qiagen's AllPrep DNA/RNA Mini Kit. RNA sequencing libraries were constructed using the NEBNext Ultra II RNA Library Prep Kit and sequenced with a single-end read length of 110 bases on an Illumina NovaSeq platform. Reduced representation bisulfite sequencing (RRBS) libraries were prepared following Msp1 digestion, bisulfite conversion, and PCR amplification, and sequenced with the same platform. The resulting RNA-seq and RRBS datasets provide comprehensive insights into gene expression and DNA methylation changes associated with epileptogenesis across these models.