Transfer of glycogen-derived lactate from astrocytes to axons via specific monocarboxylate transporters supports mouse optic nerve activity

Selva Baltan Tekkök, Angus M. Brown, Ruth Westenbroek, Luc Pellerin, Bruce R. Ransom

Research output: Contribution to journalArticlepeer-review

192 Scopus citations


It is hypothesized that L-lactate derived from astrocyte glycogen sustains axon excitability in mouse optic nerve (MON). This theory was tested by using a competitive antagonist of L-lactate transport and immunocytochemistry to determine whether transport proteins are appropriately distributed in adult MON. L-lactate sustained the compound action potential (CAP), indicating that exogenous L-lactate was an effective energy substrate. During 60 min of aglycemia, the CAP persisted for 30 min, surviving on a glycogen-derived substrate (probably lactate), before failing. After failing, the CAP could be partially rescued by restoring 10 mM glucose or 20 mM L-lactate. Aglycemia in the presence of 20 mM D-lactate, a metabolically inert but transportable monocarboxylate, resulted in accelerated CAP decline compared with aglycemia alone, suggesting that D-lactate blocked the axonal uptake of glycogen-derived L-lactate, speeding the onset of energy failure and loss of the CAR The CAP was maintained for up to 2 hr when exposed to 20% of normal bath glucose (i.e., 2 mM). To test whether glycogen-derived L-lactate "supplemented" available glucose (2 mM) in supporting metabolism, L-lactate uptake into axons was reduced by the competitive inhibitor D-lactate. Indeed, in the presence of 20 mM D-lactate, the CAP was lost more rapidly in MONs bathed in 2 mM glucose artificial cerebrospinal fluid. Immunocytochemical staining demonstrated cell-specific expression of monocarboxylate transporter (MCT) subtypes, localizing MCT2 predominantly to axons and MCT1 predominantly to astrocytes, supporting the idea that L-lactate is released from astrocytes and taken up by axons as an energy source for sustaining axon excitability.

Original languageEnglish (US)
Pages (from-to)644-652
Number of pages9
JournalJournal of Neuroscience Research
Issue number5
StatePublished - Sep 1 2005
Externally publishedYes


  • Glucose
  • Glycogen
  • L-lactate
  • Mouse optic nerve

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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