The role of GABAB receptors in oligodendrocyte precursor cells for epileptogenesis

• Applicant: Xianshu Bai, Ph.D.
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 523982092

Epilepsy is often accompanied with compromised excitation and inhibition as well as aberrant myelination. Previously, we have demonstrated that oligodendrocyte precursor cells (OPCs) are indispensable for correct cortical inhibition. OPCs sense GABA via GABABRs and release TWEAK (TNF-like weak inducer of apoptosis) to eliminate interneurons during development and optimizing interneuron density, activity and myelination. Our ongoing preliminary work suggests that the loss of GABABRs expressed by OPCs (OPC-GABABRs) can ameliorate the epileptic outcome. Now, we hypothesize that GABABR/TWEAK mediated interneuron-OPC communication deteriorates the epileptic outcome. In this proposal, we aim to reveal the molecular signalling pathway that is regulated during epileptogenesis by OPC-GABABRs. We will utilize OPC-GABABR conditional knock out mice and investigate OPCs and interneurons, as well as neural network activity by molecular biology, RNA sequencing, electrophysiology, electroencephalography and pharmacological intervention in a mouse model of temporal lobe epilepsy. Expected results will be compared to data obtained by an immunohistological analysis of epileptic patient specimen. Thereby, we may provide a novel insight for therapeutic target of epilepsy.

• DFG Programme: Research Grants