Energy transfer from astrocytes to axons: The role of CNS glycogen

Angus M. Brown, Selva Baltan Tekkök, Bruce R. Ransom

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

Abstract

We tested the hypothesis that astrocytic glycogen supports axon function under both pathological and physiological conditions. Functional activity of the rat (RON) or mouse optic nerve (MON), representative central white matter tracts, was assessed electrophysiologically as the area under the supramaximal compound action potential (CAP). During aglycaemia the CAP area of rodent optic nerve persisted for up to 30 min, after which the CAP rapidly failed. Glycogen content measured biochemically during the aglycaemic insult fell with a time course compatible with its rapid degradation in the absence of glucose. Pharmacological up-regulation of glycogen content prior to the aglycaemic insult with incubation in hyperglycaemic ambient glucose delayed CAP failure, whereas down-regulation of glycogen content induced by nor-adrenaline accelerated CAP failure. Inhibiting lactate transfer between astrocytes and axons during aglycaemia, where glycogen is the only utilisable energy reserve, resulted in accelerated CAP failure, implying that glycogen-derived lactate supports function when exogenous energy metabolites are withdrawn. Under normoglycaemic conditions glycogen content decreased during high frequency axon discharge, although CAP function was fully maintained. Both prior depletion of glycogen content, or blocking axonal lactate uptake rendered nerves incapable of fully supporting CAP function during high frequency firing in the presence of normoglycaemic glucose. These results indicated that during aglycaemia and increased metabolic demand, astrocytic glycogen was degraded to form lactate, which was used as a supplemental energy source when ambient normoglycaemic glucose was incapable of meeting immediate tissue energy demands.

Original languageEnglish (US)
Pages (from-to)529-536
Number of pages8
JournalNeurochemistry International
Volume45
Issue number4
DOIs
StatePublished - Sep 2004
Externally publishedYes

Keywords

  • Glycogen glucose
  • Lactate aglycaemia
  • Stimulus

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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