Astrocytic transformation as a driver of encephalitis-triggered epilepsy

• Applicants: Professor Dr. Christian Henneberger; Professorin Dr. Susanne Schoch McGovern; Professor Dr. Michael Wenzel
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 580429557

Epilepsy is a prevalent neurological disorder that often develops following brain insults such as viral encephalitis. While astrocytes, a non-neuronal cell type in the brain, are known to undergo a transformation called reactive astrogliosis during epilepsy, the causal link between their morphological changes and epileptogenesis remains incompletely understood. This project investigates how rapid and long-term astrocytic remodelling contributes to the development of epilepsy, using a clinically relevant mouse model of post-encephalitic temporal lobe epilepsy (TLE) based on Theiler’s murine encephalomyelitis virus (TMEV). The project is based on our research showing that epileptiform and epileptic activity rapidly induce astrocytic structural changes via RhoA-ROCK1 signalling pathways. These changes persist after neuronal activity ceases. The project will now extend this work to investigate how astrocytic morphology evolves over time and how it correlates with epileptogenesis in vivo. There will be three main objectives. 1) Longitudinal in vivo imaging of astrocytes and EEG monitoring in TMEV-infected mice will track morphological changes during the full course of epileptogenesis. 2) Advanced microscopy and phosphoproteomic analyses will characterize structural and protein-level changes in astrocytes at key stages of disease progression. 3) The role of ROCK1 in astrocyte remodelling and epileptogenesis will be tested through astrocyte-specific gene deletions. The study will combine our expertise in astrocyte biology, epilepsy modelling, and proteomics to provide insights into how the astrocytic transformation contributes to epilepsy. The long-term goal is also to identify new molecular targets to interrupt this transformation, which will potentially offer new therapeutic approaches for epilepsy.

• DFG Programme: Research Grants