Vitamin C transport and its role in the central nervous system

Vitamin C, or ascorbic acid, is important as an antioxidant and participates in numerous cellular functions. Although it circulates in plasma in micromolar concentrations, it reaches millimolar concentrations in most tissues. These high ascorbate cellular concentrations are thought to be generated and maintained by the SVCT2 (Slc23a2), a specific transporter for ascorbate. The vitamin is also readily recycled from its oxidized forms inside cells. Neurons in the central nervous system (CNS) contain some of the highest ascorbic acid concentrations of mammalian tissues. Intracellular ascorbate serves several functions in the CNS, including antioxidant protection, peptide amidation, myelin formation, synaptic potentiation, and protection against glutamate toxicity. The importance of the SVCT2 for CNS function is supported by the finding that its targeted deletion in mice causes widespread cerebral hemorrhage and death on post-natal day 1. Neuronal ascorbate content as maintained by this protein also has relevance for human disease, since ascorbate supplements decrease infarct size in ischemia-reperfusion injury models of stroke, and since ascorbate may protect neurons from the oxidant damage associated with neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's. The aim of this review is to assess the role of the SVCT2 in regulating neuronal ascorbate homeostasis and the extent to which ascorbate affects brain function and antioxidant defenses in the CNS.