Single-Nucleus Transcriptomic Sequencing Revealed Cellular and Molecular Changes in a Pilocarpine-Induced Epilepsy Rat Model

Uncovering the underlying process of epileptogenesis is crucial for developing effective treatment strategies for epilepsy. However, the cellular and molecular changes throughout epileptogenesis are not fully understood. In this study, single-nucleus RNA sequencing was performed on the hippocampus, temporal cortex, and thalamus across the acute, latent, and chronic phases in a pilocarpine-induced rat model and controls. We created a comprehensive single-nucleus transcriptomic atlas of rat epileptogenesis, consisting of 311,177 single nuclei. Our analysis revealed distinct transcriptional signatures across the three phases and regions, including significant gene expression changes in the acute phase and critical synaptic and neural network remodeling in the thalamus during the latent phase. Notably, we identified two novel astrocyte clusters during epileptogenesis, with the EX-Astro C3-IN pathway emerging as a potential intervention target. The dataset provides a detailed understanding of the dynamic cellular and molecular landscape of epileptogenesis.