Intracellular ascorbic acid inhibits transport of glucose by neurons, but not by astrocytes
Article first published online: 5 APR 2007
Journal of Neurochemistry
Volume 102, Issue 3, pages 773–782, August 2007
How to Cite
Castro, M. A., Pozo, M., Cortés, C., García, M. d. l. A., Concha, I. I. and Nualart, F. (2007), Intracellular ascorbic acid inhibits transport of glucose by neurons, but not by astrocytes. Journal of Neurochemistry, 102: 773–782. doi: 10.1111/j.1471-4159.2007.04631.x
- Issue published online: 5 APR 2007
- Article first published online: 5 APR 2007
- Received April 18, 2006; revised manuscript received January 24, 2007; accepted February 12, 2007.
- ascorbic acid;
- glucose transporters;
- sodium–vitamin C cotransporter 2
It has been demonstrated that glutamatergic activity induces ascorbic acid (AA) depletion in astrocytes. Additionally, different data indicate that AA may inhibit glucose accumulation in primary cultures of rat hippocampal neurons. Thus, our hypothesis postulates that AA released from the astrocytes during glutamatergic synaptic activity may inhibit glucose uptake by neurons. We observed that cultured neurons express the sodium-vitamin C cotransporter 2 and the facilitative glucose transporters (GLUT) 1 and 3, however, in hippocampal brain slices GLUT3 was the main transporter detected. Functional activity of GLUTs was confirmed by means of kinetic analysis using 2-deoxy-d-glucose. Therefore, we showed that AA, once accumulated inside the cell, inhibits glucose transport in both cortical and hippocampal neurons in culture. Additionally, we showed that astrocytes are not affected by AA. Using hippocampal slices, we observed that upon blockade of monocarboxylate utilization by α-cyano-4-hydroxycinnamate and after glucose deprivation, glucose could rescue neuronal response to electrical stimulation only if AA uptake is prevented. Finally, using a transwell system of separated neuronal and astrocytic cultures, we observed that glutamate can reduce glucose transport in neurons only in presence of AA-loaded astrocytes, suggesting the essential role of astrocyte-released AA in this effect.