Vitamin C Transport and Its Role in the Central Nervous System

Abstract

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 one. 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.

Ascorbic Acid Reduces the Adverse Effects of Delayed Administration of Tissue Plasminogen Activator in a Rat Stroke Model

“…In addition to its antioxidant protection, AA participates in numerous cellular functions [33]. Although AA circulates in plasma in micromolar concentrations, it reaches millimolar concentrations in most tissues.…”

“…Neurons in the central nervous system (CNS) contain some of the highest AA concentrations of mammalian tissues. Ascorbic acid serves several functions in the CNS, including peptide amidation, myelin formation, synaptic potentiation and protection against glutamate toxicity [33]. NF-jB is a dimeric transcription factor activated by reactive oxygen species [2], and it has been shown that it up-regulates many inflammatory cytokines such as MMP-9 [34].…”

Genome-wide analysis shows association of epigenetic changes in regulators of Rab and Rho GTPases with spinal muscular atrophy severity

“…In the CNS, ascorbate has several functions including antioxidant protection, peptide amidation, myelin formation, synaptic potentiation and protection against glutamate toxicity. 52 Ascorbate has neuroprotective properties against the oxidative damage associated with different neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's disease. 52 Thus, the decreased methylation level of CpG site in the SLC23A2 gene in both groups of SMA patients, assuming there is increased expression level of this gene, might denote the SLC23A2 gene could fulfill a certain compensatory function for motor neurons and aid in their survival in SMA patients.…”

Alzheimer’s Disease: Dawn of a New Era?

“…Vitamin C: Ascorbic acid (vitamin C) is an important antioxidant in intracellular functions, with some of highest concentrations in CNS (202). It easily reacts with reactive oxygen species to neutralize their activity, and become ascorbate free radical, which is then recycled (203).…”