The Role of Astrocytes in Remyelination

Remyelination is orchestrated by several cell types in the lesion microenvironment, including OPCs, microglia, infiltrating macrophages, regulatory T cells, pericytes, axons, and astrocytes. Reactive astrocytes are characterized by a transient upregulation in over a thousand genes, many of which are proregenerative, whereas scar-forming astrocytes result in significant tissue reorganization, fail to resolve, and are a consequence of regeneration failure. Reactive astrocytes secrete several classes of regenerative and inhibitory molecules that are likely synchronized to the tightly regulated kinetics of remyelination. Aging exerts a negative influence on the astrocyte response, which may, in turn, impact remyelination. Remyelination is the regeneration of myelin sheaths following demyelination. This regenerative process is critical for the re-establishment of axonal conduction velocity and metabolic support to the axons. Successful remyelination in the CNS generally depends on the activation, proliferation, and differentiation of oligodendrocyte progenitor cells (OPCs). However, other cell types play critical roles in establishing where a lesion is conducive for regeneration. In the last few years, several studies have described beneficial and detrimental roles played by astrocytes in remyelination. This review will discuss recent developments in the concept of astrocyte reactivity, what is known about the astrocytic contribution to remyelination, and highlight future avenues of investigation. Remyelination is the regeneration of myelin sheaths following demyelination. This regenerative process is critical for the re-establishment of axonal conduction velocity and metabolic support to the axons. Successful remyelination in the CNS generally depends on the activation, proliferation, and differentiation of oligodendrocyte progenitor cells (OPCs). However, other cell types play critical roles in establishing where a lesion is conducive for regeneration. In the last few years, several studies have described beneficial and detrimental roles played by astrocytes in remyelination. This review will discuss recent developments in the concept of astrocyte reactivity, what is known about the astrocytic contribution to remyelination, and highlight future avenues of investigation.