Astrocytic aerobic glycolysis provides lactate to support neuronal oxidative metabolism in the hippocampus

Cândida Dias; Eliana Fernandes; Rui M. Barbosa; João Laranjinha; Ana Ledo

doi:10.1002/biof.1951

journal article Open Access Apr 17, 2023

Astrocytic aerobic glycolysis provides lactate to support neuronal oxidative metabolism in the hippocampus

Cândida Dias Eliana Fernandes Rui M. Barbosa João Laranjinha Ana Ledo

BioFactors Vol. 49 No. 4 pp. 875-886 · Wiley

View at Publisher Save 10.1002/biof.1951

Abstract

AbstractUnder physiological conditions, the energetic demand of the brain is met by glucose oxidation. However, ample evidence suggests that lactate produced by astrocytes through aerobic glycolysis may also be an oxidative fuel, highlighting the metabolic compartmentalization between neural cells. Herein, we investigate the roles of glucose and lactate in oxidative metabolism in hippocampal slices, a model that preserves neuron–glia interactions. To this purpose, we used high‐resolution respirometry to measure oxygen consumption (O2 flux) at the whole tissue level and amperometric lactate microbiosensors to evaluate the concentration dynamics of extracellular lactate. We found that lactate is produced from glucose and transported to the extracellular space by neural cells in hippocampal tissue. Under resting conditions, endogenous lactate was used by neurons to support oxidative metabolism, which was boosted by exogenously added lactate even in the presence of excess glucose. Depolarization of hippocampal tissue with high K+ significantly increased the rate of oxidative phosphorylation, which was accompanied by a transient decrease in extracellular lactate concentration. Both effects were reverted by inhibition of the neuronal lactate transporter, monocarboxylate transporters 2 (MCT2), supporting the concept of an inward flux of lactate to neurons to fuel oxidative metabolism. We conclude that astrocytes are the main source of extracellular lactate which is used by neurons to fuel oxidative metabolism, both under resting and stimulated conditions.

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Details

Published: Apr 17, 2023
Vol/Issue: 49(4)
Pages: 875-886
License: View

Authors

C

Cândida Dias