Genetic ablation of GABA _B receptors from oligodendrocyte precursor cells protects against demyelination in the mouse spinal cord

GABAergic signaling and GABA _B receptors play crucial roles in regulating the physiology of oligodendrocyte-lineage cells, including their proliferation, differentiation, and myelination. Therefore, they are promising targets for studying how spinal oligodendrocyte precursor cells (OPCs) respond to injuries and neurodegenerative diseases like multiple sclerosis. Taking advantage of the temporally controlled and cell-specific genetic removal of GABA _B receptors from OPCs, our investigation addresses their specific influence on OPC behavior in the gray and white matter of the mouse spinal cord. Our results show that while GABA _B receptors do not significantly alter OPC cell proliferation and differentiation under physiological conditions, they distinctly regulate the Ca ²⁺ signaling of OPCs. In addition, we investigate the impact of OPC-GABA _B receptors in two models of toxic demyelination, namely the cuprizone and the lysolecithin models. The genetic removal of OPC-GABA _B receptors protects against demyelination and oligodendrocyte loss. Additionally, we observe enhanced resilience to cuprizone-induced pathological alterations in OPC Ca ²⁺ signaling. Our results provide valuable insights into the potential therapeutic implications of manipulating GABA _B receptors in spinal cord OPCs and deepen our understanding of the interplay between GABAergic signaling and spinal cord OPCs, providing a basis for future research.