Intracellular ascorbic acid inhibits transport of glucose by neurons, but not by astrocytes.
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 alpha-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.
Castro
Maite A
MA
Instituto de Bioquímica, Facultad de Ciencias Biológicas, Universidad Austral de Chile, Valdivia, Chile.
Pozo
Miguel
M
Cortés
Christian
C
García
María de Los Angeles
Mde L
Concha
Ilona I
II
Nualart
Francisco
F
D000818:Animals; D000831:Animals, Newborn; D001205:Ascorbic Acid / Q000378:metabolism* / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D004558:Electric Stimulation; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D027501:Monocarboxylic Acid Transporters; D029363:Organic Anion Transporters, Sodium-Dependent; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D018698:Glutamic Acid; D005947:Glucose; D001205:Ascorbic Acid