Neuronal-glial glucose oxidation and glutamatergic - GABAergic function

Prior C-13 magnetic resonance spectroscopy (MRS) experiments, which simultaneously measured in vivo rates of total glutamate-glutamine cycling (V-cyc(tot)) and neuronal glucose oxidation (CMRglc((ox))(,N)), revealed a linear relationship between these fluxes above isoelectricity, with a slope of similar to 1. In vitro glial culture studies examining glutamate uptake indicated that glutamate, which is cotransported with Na+, stimulated glial uptake of glucose and release of lactate. These in vivo and in vitro results were consolidated into a model: recycling of one molecule of neurotransmitter between glia and neurons was associated with oxidation of one glucose molecule in neurons; however, the glucose was taken up only by glia and all the lactate (pyruvate) generated by glial glycolysis was transferred to neurons for oxidation. The model was consistent with the 1: 1 relationship between Delta CMRglc(ox),N and Delta V-cyc(tot) measured by C-13 MRS. However, the model could not specify the energetics of glia and gamma-amino butyric acid (GABA) neurons because quantitative values for these pathways were not available. Here, we review recent C-13 and C-14 tracer studies that enable us to include these fluxes in a more comprehensive model. The revised model shows that glia produce at least 8% of total oxidative ATP and GABAergic neurons generate similar to 18% of total oxidative ATP in neurons. Neurons produce at least 88% of total oxidative ATP, and take up similar to 26% of the total glucose oxidized. Glial lactate (pyruvate) still makes the major contribution to neuronal oxidation, but similar to 30% less than predicted by the prior model. The relationship observed between Delta CMRglc(ox),N and Delta V-cyc(tot) is determined by glial glycolytic ATP as before. Quantitative aspects of the model, which can be tested by experimentation, are discussed.