Ascorbate transport by primary cultured neurons and its role in neuronal function and protection against excitotoxicity

Shenfeng Qiu, Ying Li, Edwin J. Weeber, James M. May

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Neurons maintain relatively high intracellular concentrations of ascorbic acid, which is achieved primarily by the activity of the sodium-dependent vitamin C transporter SVCT2. In this work, we studied the mechanisms by which neuronal cells in culture transport and maintain ascorbate as well as whether this system contributes to maturation of neuronal function and cellular defense against oxidative stress and excitotoxic injury. We found that the SVCT2 helps to maintain high intracellular ascorbate levels, normal ascorbate transport kinetics, and activity-dependent ascorbate recycling. Immunocytochemistry studies revealed that SVCT2 is expressed primarily in the axons of mature hippocampal neurons in culture. In the absence of SVCT2, hippocampal neurons exhibited stunted neurite outgrowth, less glutamate receptor clustering, and reduced spontaneous neuronal activity. Finally, hippocampal cultures from SVCT2-deficient mice showed increased susceptibility to oxidative damage and N-methyl-D-aspartate-induced excitotoxicity. Our results revealed that maintenance of intracellular ascorbate as a result of SVCT2 activity is crucial for neuronal development, functional maturation, and antioxidant responses.

Original languageEnglish (US)
Pages (from-to)1046-1056
Number of pages11
JournalJournal of Neuroscience Research
Volume85
Issue number5
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

Keywords

  • Ascorbic acid
  • Axonal transporter
  • GSH
  • Glutamate receptor
  • Oxidant stress
  • SVCT2

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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