Glutamate uptake into astrocytes stimulates aerobic glycolysis: A mechanism coupling neuronal activity to glucose utilization

Luc Pellerin*, Pierre Magistretti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1923 Scopus citations

Abstract

Glutamate, released at a majority of excitatory synapses in the central nervous system, depolarizes neurons by acting at specific receptors. Its action is terminated by removal from the synaptic cleft mostly via Na+- dependent uptake systems located on both neurons and astrocytes. Here we report that glutamate, in addition to its receptor-mediated actions on neuronal excitability, stimulates glycolysis-i.e., glucose utilization and lactate production-in astrocytes. This metabolic action is mediated by activation of a Na+-dependent uptake system and not by interaction with receptors. The mechanism involves the Na+/K+-ATPase, which is activated by an increase in the intracellular concentration of Na+ cotransported with glutamate by the electrogenic uptake system. Thus, when glutamate is released from active synapses and taken up by astrocytes, the newly identified signaling pathway described here would provide a simple and direct mechanism to tightly couple neuronal activity to glucose utilization. In addition, glutamate-stimulated glycolysis is consistent with data obtained from functional brain imaging studies indicating local nonoxidative glucose utilization during physiological activation.

Original languageEnglish (US)
Pages (from-to)10625-10629
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number22
DOIs
StatePublished - Oct 25 1994

Keywords

  • 2-deoxyglucose
  • K-ATPase
  • Na
  • glutamate transporter
  • magnetic resonance imaging
  • positron-emission tomography

ASJC Scopus subject areas

  • General

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