Astrocyte activation via Stat3 signalling determines the balance of oligodendrocyte versus Schwann cell remyelination

Abstract

Remyelination within the Central Nervous System (CNS) is most often the result of oligodendrocyte progenitor cells (OPCs) differentiating into myelin-forming oligodendrocytes. In some cases, however, Schwann cells, the peripheral nervous system myelinating glia, are found remyelinating demyelinated regions of the CNS. The reason for this peripheral type remyelination in the CNS and what governs it is unknown. Here we have used a conditional astrocytic phosphorylated Signal Transducer and Activator of Transcription 3 knockout (GFAP-STAT3-CKO) mouse model to investigate the effect of abrogating astrocyte activation on remyelination following lysolecithin-induced demyelination of spinal cord white matter. We show that oligodendrocyte mediated remyelination is decreased and Schwann cell remyelination is increased in lesioned knockout mice in comparison to lesioned controls. Our study shows that astrocyte activation plays a crucial role in the balance between Schwann cell and oligodendrocyte remyelination in the CNS, and provides further insight into how Schwann cells remyelinate CNS axons.