title: Neuronal-glial glucose oxidation and glutamatergic-GABAergic function.
abstract: Prior 13C magnetic resonance spectroscopy (MRS) experiments, which simultaneously measured in vivo rates of total glutamate-glutamine cycling (V(cyc(tot))) and neuronal glucose oxidation (CMR(glc(ox), N)), revealed a linear relationship between these fluxes above isoelectricity, with a slope of approximately 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 DeltaCMR(glc(ox), N) and DeltaV(cyc(tot)) measured by 13C 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 13C and 14C 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 approximately 18% of total oxidative ATP in neurons. Neurons produce at least 88% of total oxidative ATP, and take up approximately 26% of the total glucose oxidized. Glial lactate (pyruvate) still makes the major contribution to neuronal oxidation, but approximately 30% less than predicted by the prior model. The relationship observed between DeltaCMR(glc(ox), N) and DeltaV(cyc(tot)) is determined by glial glycolytic ATP as before. Quantitative aspects of the model, which can be tested by experimentation, are discussed.
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. fahmeed.hyder@yale.edu
authors.forename: Fahmeed
authors.initials: F
authors.lastname: Hyder
authors.forename: Anant B
authors.initials: AB
authors.lastname: Patel
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Rothman
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Behar
authors.forename: Robert G
authors.initials: RG
authors.lastname: Shulman
mesh_terms: D000818:Animals; D005947:Glucose / Q000737:chemistry / Q000378:metabolism*; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008954:Models, Biological; D009457:Neuroglia / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D012680:Sensitivity and Specificity; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005947:Glucose