Optic nerve energy metabolism: the role of astrocyte glycogen

Abstract

SummaryGlycogen is a glucose storage molecule. We studied the physiology and functions of glycogen in CNS white matter using acutely isolated mouse optic nerve (MON), a typical CNS white matter tract. Glycogen is present in MON astrocytes. Aglycemia caused loss of the stimulus evoked compound action potential (CAP) after ~15 min. CAP decline coincided with exhaustion of usable tissue glycogen. Increasing glycogen content prolonged the latency to decline onset and, conversely, decreasing glycogen shortened this latency. Metabolic support provided by glycogen during aglycemia was abolished by an inhibitor of glycogen breakdown (DAB). The MON has a high resting level of extracellular lactate (~0.6 mM). The metabolic support provided by glycogen during aglycemia is abolished by an inhibitor of glycogen breakdown (DAB) in MON. Both tissues exhibit high levels of extracellular lactate ([Lactate−]o), up to 50% of which derives from glycogen. During aglycemia, glycogen in astrocytes is metabolized to lactate and ‘shuttled’ to axons (and possibly oligodendrocytes) to support oxidative energy metabolism. Glycogen breakdown and lactate transport to axons is also needed to sustain brief periods of intense axonal discharge.