The Role of Astrocytes in Multiple Sclerosis

Abstract

The role traditionally assigned to astrocytes in the pathogenesis of multiple sclerosis (MS) lesions has been the formation of the glial scar once inflammation has subsided. Astrocytes are now recognized to be early and highly active players during lesion formation and key for providing peripheral immune cells access to the central nervous system. Here, we review the role of astrocytes in the formation and evolution of MS lesions, including the recently described functional polarization of astrocytes, discuss prototypical pathways for astrocyte activation, and summarize mechanisms by which MS treatments affect astrocyte function.

Keywords: NF-κB; astrocytes; leukocyte recruitment; multiple sclerosis; neuroinflammation; risk variant.

Figure 1

Schematic of the glia limitans and a reactive astrocyte in multiple sclerosis (MS), indicating secretion of cytokines, recruitment of leukocytes across the blood–brain barrier, and upregulation of selected receptors that contribute to astrocyte responses and metabolic changes. Inset image shows a reactive hypertrophic astrocyte at the active rim of an MS lesion containing myelin debris within lysosomal ring structures [glial fibrillary acidic protein (GFAP), cyan; myelin proteolipid protein (PLP), red; lysosomal-associated membrane protein 1 (LAMP1), white]. Scale bar = 10 µm. The inset image was reproduced from Figure 1 of Ponath et al. (17) with the permission of Brain.

Figure 2

Intracellular astrocytic signaling pathways and effects of multiple sclerosis (MS) treatments on signaling function. Inset shows schematic of the effect of MS risk variant, rs7665090, on NF-κB subunit expression and NF-κB signaling.