Neuronal-glial glucose oxidation and glutamatergic-GABAergic function

Fahmeed Hyder, Anant B. Patel, Albert Gjedde, Douglas L. Rothman, Kevin L. Behar, Robert G. Shulman

Research output: Contribution to journalReview articlepeer-review

295 Scopus citations


Prior 13C magnetic resonance spectroscopy (MRS) experiments, which simultaneously measured in vivo rates of total glutamate-glutamine cycling (Vcyc(tot)) and neuronal glucose oxidation (CMR glc(ox), N), revealed a linear relationship between these fluxes above isoelectricity, with a slope of ∼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 ΔCMRglc(ox), N and ΔV cyc(tot) measured by 13C MRS. However, the model could not specify the energetics of glia and γ-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 ∼18% of total oxidative ATP in neurons. Neurons produce at least 88% of total oxidative ATP, and take up ∼26% of the total glucose oxidized. Glial lactate (pyruvate) still makes the major contribution to neuronal oxidation, but ∼30% less than predicted by the prior model. The relationship observed between ΔCMRglc(ox), N and ΔV cyc(tot) is determined by glial glycolytic ATP as before. Quantitative aspects of the model, which can be tested by experimentation, are discussed.

Original languageEnglish (US)
Pages (from-to)865-877
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number7
StatePublished - Jun 19 2006
Externally publishedYes


  • Baseline
  • Neuroimaging
  • Oxygen
  • Perfusion
  • Signaling
  • fMRI

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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