Hippocampal gene expression changes associated with sequential behavioral training in a temporal lobe epilepsy rat model☆

The transcriptional mechanisms underlying impaired hippocampal-dependent memory seen in temporal lobe epilepsy (TLE) have been extensively studied in rodent models. While cognitive testing in these models often involves multiple behavioral tasks, the impact of sequential behavioral testing (SBT) on gene transcription changes in epilepsy remains poorly understood. This study utilized the Kainic Acid (KA) TLE rodent model to examine hippocampal gene expression changes influenced by SBT. Our findings indicate reduced anxiety-related behavior, along with impaired spatial and recognition memory and fear memory in epileptic animals. Quantitative PCR (qPCR) analysis revealed an increase in BDNF, dFosB, Tet2, and Tet3 expression in the epilepsy-SBT group compared to control-SBT, while there was a reduction in Npas4 and Egr4 expression. Immunohistochemistry (IHC) showed that in epileptic animals, performing SBT reversed the loss of 5-hydroxymethylcytosine (5hmC) in the dorsal hippocampus compared to that seen in home-caged (HC) epileptic animals, and this reversal was neuron-driven. These findings highlight the complex interplay between gene transcription and epigenetic regulation during SBT enrichment in the context of epilepsy.