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

Qiu S, Li L, Weeber EJ, May JM
J Neurosci Res. 2007 85 (5): 1046-56

PMID: 17304569 · DOI:10.1002/jnr.21204

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.

(c) 2007 Wiley-Liss, Inc.

MeSH Terms (23)

Animals Antioxidants Ascorbic Acid Axons Biological Transport, Active Brain Cell Differentiation Cells, Cultured Cerebral Cortex Cytoprotection Hippocampus Mice Mice, Inbred C57BL Mice, Knockout N-Methylaspartate Neurites Neurons Neurotoxins Organic Anion Transporters, Sodium-Dependent Oxidative Stress Receptors, Glutamate Sodium-Coupled Vitamin C Transporters Symporters

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