TY - JOUR

T1 - Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter

AU - Brown, Angus M

AU - Sickmann, Helle M

AU - Fosgerau, Keld

AU - Lund, Trine Meldgaard

AU - Schousboe, Arne

AU - Waagepetersen, Helle S

AU - Ransom, Bruce R

N1 - (c) 2004 Wiley-Liss, Inc.

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - Action Potentials

KW - Analysis of Variance

KW - Animals

KW - Animals, Newborn

KW - Astrocytes

KW - Cells, Cultured

KW - Cerebellum

KW - Drug Interactions

KW - Electric Stimulation

KW - Glucose

KW - Glycogen

KW - Glycogen Phosphorylase

KW - Hyperglycemia

KW - Hypoglycemia

KW - Imino Pyranoses

KW - Male

KW - Mice

KW - Models, Biological

KW - Optic Nerve

KW - Oxygen

KW - Piperidines

KW - Reaction Time

U2 - 10.1002/jnr.20335

DO - 10.1002/jnr.20335

M3 - Journal article

C2 - 15578727

VL - 79

SP - 74

EP - 80

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 1-2

ER -