Changes in glucose uptake rather than lactate shuttle take center stage in subserving neuroenergetics: Evidence from mathematical modeling

Mauro Dinuzzo, Silvia Mangia, Bruno Maraviglia, Federico Giove

Research output: Contribution to journalArticlepeer-review

Abstract

In this paper, we combined several mathematical models of cerebral metabolism and nutrient transport to investigate the energetic significance of metabolite trafficking within the brain parenchyma during a 360-secs activation. Glycolytic and oxidative cellular metabolism were homogeneously modeled between neurons and astrocytes, and the stimulation-induced neuronal versus astrocytic Na inflow was set to 3:1. These assumptions resemble physiologic conditions and are supported by current literature. Simulations showed that glucose diffusion to the interstitium through basal lamina dominates the provision of the sugar to both neurons and astrocytes, whereas astrocytic endfeet transfer less than 4% of the total glucose supplied to the tissue. Neuronal access to paracellularly diffused glucose prevails even after halving (doubling) the ratio of neuronal versus astrocytic glycolytic (oxidative) metabolism, as well as after reducing the neuronal versus astrocytic Na+ inflow to a nonphysiologic value of 1:1. Noticeably, displaced glucose equivalents as intercellularly shuttled lactate account for ∼ 6% to 7% of total brain glucose uptake, an amount comparable with the concomitant drainage of the monocarboxylate by the bloodstream. Overall, our results suggest that the control of carbon recruitment for neurons and astrocytes is exerted at the level of glucose uptake rather than that of lactate shuttle.

Original languageEnglish
Pages (from-to)586-602
Number of pages17
JournalJournal of Cerebral Blood Flow and Metabolism
Volume30
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • Brain activation
  • Energy metabolism
  • Mathematical modeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

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