Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter

Angus M Brown, Helle M Sickmann, Keld Fosgerau, Trine Meldgaard Lund, Arne Schousboe, Helle S Waagepetersen, Bruce R Ransom

    129 Citations (Scopus)

    Abstract

    We tested the hypothesis that inhibiting glycogen degradation accelerates compound action potential (CAP) failure in mouse optic nerve (MON) during aglycemia or high-intensity stimulation. Axon function was assessed as the evoked CAP, and glycogen content was measured biochemically. Isofagomine, a novel inhibitor of central nervous system (CNS) glycogen phosphorylase, significantly increased glycogen content under normoglycemic conditions. When MONs were bathed in artificial cerebrospinal fluid (aCSF) containing 10 mM glucose, the CAP failed 16 min after exposure to glucose-free aCSF. MONs bathed in aCSF plus isofagomine displayed accelerated CAP failure on glucose removal. Similar results were obtained in MONs bathed in 30 mM glucose, which increased baseline glycogen concentration. The ability of isofagomine to increase glycogen content thus was not translated into delayed CAP failure. This is likely due to the inability of the tissue to metabolize glycogen in the presence of isofagomine, highlighting the importance of glycogen in sustaining neural function during aglycemia. The hypothesis that glycogen breakdown supports intense neural activity was tested by blocking glycogen breakdown during periods of high-frequency stimulation. The CAP area declined more rapidly when glycogen metabolism was inhibited by isofagomine, explicitly showing an important physiological role for glycogen metabolism during neural activity.
    Original languageEnglish
    JournalJournal of Neuroscience Research
    Volume79
    Issue number1-2
    Pages (from-to)74-80
    Number of pages7
    ISSN0360-4012
    DOIs
    Publication statusPublished - 2005

    Keywords

    • Action Potentials
    • Analysis of Variance
    • Animals
    • Animals, Newborn
    • Astrocytes
    • Cells, Cultured
    • Cerebellum
    • Drug Interactions
    • Electric Stimulation
    • Glucose
    • Glycogen
    • Glycogen Phosphorylase
    • Hyperglycemia
    • Hypoglycemia
    • Imino Pyranoses
    • Male
    • Mice
    • Models, Biological
    • Optic Nerve
    • Oxygen
    • Piperidines
    • Reaction Time

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