High concentrations of vitamin C are found in the central nervous system. In Science Signaling, Portugal et al. show that brain-resident microglia require vitamin C for homeostasis. Microglia import extracellular ascorbate, the reduced form of vitamin C, via sodium–vitamin C cotransporter 2 (SVCT2). Intracellular ascorbate reduces activation and nuclear translocation of the transcription factor NF-κB, thereby limiting the production of proinflammatory mediators. Conversely, exposure to lipopolysaccharide activates microglia by inducing SVCT2 internalization and lysosomal degradation by a mechanism that involves Src kinase and caveolin-1. Reduced expression or inhibition of SVCT2 also activates microglia, thus leading to increased expression of tumor necrosis factor, interleukin 6 (IL-6), IL-1β, MHC class II molecules, TREM2, iNOS and inflammatory chemokines. The question of whether loss of SVCT2 is involved in neuroinflammatory disease deserves further attention.

Sci. Signal. 10, eaal2005 (2017)