Basal Sodium-Dependent Vitamin C Transporter 2 polarization in choroid plexus explant cells in normal or scorbutic conditions

Sci Rep. 2019 Oct 8;9(1):14422. doi: 10.1038/s41598-019-50772-2.

Abstract

Vitamin C is incorporated into the cerebrospinal fluid (CSF) through choroid plexus cells. While the transfer of vitamin C from the blood to the brain has been studied functionally, the vitamin C transporter, SVCT2, has not been detected in the basolateral membrane of choroid plexus cells. Furthermore, it is unknown how its expression is induced in the developing brain and modulated in scurvy conditions. We concluded that SVCT2 is intensely expressed in the second half of embryonic brain development and postnatal stages. In postnatal and adult brain, SVCT2 is highly expressed in all choroidal plexus epithelial cells, shown by colocalization with GLUT1 in the basolateral membranes and without MCT1 colocalization, which is expressed in the apical membrane. We confirmed that choroid plexus explant cells (in vitro) form a sealed epithelial structure, which polarized basolaterally, endogenous or overexpressed SVCT2. These results are reproduced in vivo by injecting hSVCT2wt-EYFP lentivirus into the CSF. Overexpressed SVCT2 incorporates AA (intraperitoneally injected) from the blood to the CSF. Finally, we observed in Guinea pig brain under scorbutic condition, that normal distribution of SVCT2 in choroid plexus may be regulated by peripheral concentrations of vitamin C. Additionally, we observed that SVCT2 polarization also depends on the metabolic stage of the choroid plexus cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / metabolism*
  • Blood-Brain Barrier / growth & development
  • Blood-Brain Barrier / metabolism
  • Brain / growth & development
  • Brain / metabolism*
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Choroid Plexus / metabolism
  • Embryonic Development / genetics
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation, Developmental / genetics
  • Glucose Transporter Type 1 / blood*
  • Guinea Pigs
  • Mice
  • Monocarboxylic Acid Transporters / genetics
  • Neurons / metabolism
  • Sodium-Coupled Vitamin C Transporters / blood*
  • Sodium-Coupled Vitamin C Transporters / cerebrospinal fluid
  • Swine
  • Symporters / genetics

Substances

  • Glucose Transporter Type 1
  • Monocarboxylic Acid Transporters
  • Slc23a2 protein, mouse
  • Sodium-Coupled Vitamin C Transporters
  • Symporters
  • monocarboxylate transport protein 1
  • Ascorbic Acid