Activated astrocytes increase dehydroascorbic acid uptake, changing intracellular metabolism and vitamin C recycling...

Oxidative damage in neurodegenerative diseases activates astrocytes and perturbs antioxidant defenses. Vitamin C is the principal antioxidant in the brain. Ascorbic acid (AA, reduced form) is taken up by neurons via the sodium/vitamin C transporter 2 (SVCT2). Astrocytes take up only the oxidized form of vitamin C, dehydroascorbic acid (DHA), through glucose transporters (GLUT). AA is recycled between neurons and astrocytes, preserving antioxidant capacity and maintaining physiological DHA levels. We postulate that AA recycling modulates astrocyte energy and redox metabolism. We therefore examined the effects of AA and DHA accumulation on glycolysis, pentose phosphate pathway (PPP) activity, and glutathione (GSH) concentrations in activated astrocytes. Culture time negatively modulated DHA recycling. At 15 days in vitro (DIV), astrocytes efficiently took up physiological DHA and reduced it to AA, enhancing redox metabolism, stimulating PPP activity, and increasing intracellular GSH. At 30 DIV (cells positive for activation markers), astrocytes took up higher amounts of DHA but reduced it inefficiently; at this time point, the glycolytic rate was unchanged, PPP activity was inhibited, and GSH decreased. In both 15- and 30-DIV astrocytes, DHA stimulated lactate uptake. We propose that 30-DIV astrocytes constitute a cellular model of reactive astrocytes with impaired AA recycling, ultimately altering glycolytic and antioxidant function.