Ying Wang1  · Yue Wang2  · Fei Yu1  · Yidi Liu1  · Xin Liu3,4 · Zhengxu Cai1

1 Department of Neurology, The First Afliated Hospital of Dalian Medical University, Dalian 116011, China 

2 State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao 51900, China 

3 Shanxi Medical University, Taiyuan 030607, China 

4 University of Chinese Academy of Sciences, Beijing 100049, China

Abstract

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.

Keywords

Epileptogenesis; Single-nucleus RNA sequencing; Pilocarpine-induced epilepsy rat model; Latent phase; Astrocytes

[SpringerLink]