Energy Substrates for Neurons during Neural Activity: A Critical Review of the Astrocyte-Neuron Lactate Shuttle Hypothesis

Ching Ping Chi, Eugene L. Roberts

Research output: Contribution to journalReview article

229 Scopus citations

Abstract

Glucose had long been thought to fuel oxidative metabolism in active neurons until the recently proposed astrocyte-neuron lactate shuttle hypothesis (ANLSH) challenged this view. According to the ANLSH, activity-induced uptake of glucose takes place predominantly in astrocytes, which metabolize glucose anaerobically. Lactate produced from anaerobic glycolysis in astrocytes is then released from astrocytes and provides the primary metabolic fuel for neurons. The conventional hypothesis asserts that glucose is the primary substrate for both neurons and astrocytes during neural activity and that lactate produced during activity is removed mainly after neural activity. The conventional hypothesis does not assign any particular fraction of glucose metabolism to the aerobic or anaerobic pathways. In this review, the authors discuss the theoretical background and critically review the experimental evidence regarding these two hypotheses. The authors conclude that the experimental evidence for the ANLSH is weak, and that existing evidence and theoretical considerations support the conventional hypothesis.

Original languageEnglish (US)
Pages (from-to)1263-1281
Number of pages19
JournalJournal of Cerebral Blood Flow and Metabolism
Volume23
Issue number11
DOIs
StatePublished - Nov 2003

Keywords

  • Brain
  • Energy metabolism
  • Glucose
  • Glycolysis
  • Lactate
  • Oxidative phosphorylation

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

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