Transcriptomic profile of the hippocampus after status epilepticus in wildtype and EZH2 neuronal knockout mice.

EZH2 is a key epigenetic regulator that catalyzes histone methylation to effect transcriptional repression. Preliminary data suggested that EZH2 induction is a protective response mounted by the brain in response to seizures. To investigate the impact of EZH2 deletion in hippocampal neurons under pathological conditions, we generated whole transcriptome profiles using RNA sequencing in saline and kainate-treated wild-type (EZH2nWT) mice, as well as homozygous EZH2 neuronal knockout (EZH2nHom) mice. Our results reveal significant alterations in gene expression patterns in the hippocampus of EZH2nHom compared to EZH2nWT mice, particularly following kainate-induced seizures. Overall, our study provides valuable insights into the transcriptional changes induced by EZH2 deletion in hippocampal neurons, highlighting its importance in regulating gene expression in response to epileptogenic insults. To investigate the protective role of EZH2 induction after seizures, we used Synapsin1-Cre to generate EZH2 wildtype (EZH2nWT) and conditional neuronal knockout mice (EZH2nHom) on a C57BL6 background. We used a repeated low-dose kainate model to induce status epilepticus, injecting controls with saline to produce four experimental conditions: saline:WT, kainate:WT, saline:EZH2nHom, kainate:EZH2nHom. Whole hippocampi were harvested four days after induction of status epilepticus.