The Role of Nervous System Glycogen during Hypoglycemia

The mammalian brain contains glycogen but in concentrations much lower than in the liver and skeletal muscle, thus a role as a functional energy reserve has been dismissed. Glycogen in the central nervous system is located in astrocytes in the adult, and in the peripheral nervous system is expressed in myelinating Schwann cells. During periods of experimental aglycemia in rodent optic nerve, a model of central white matter, the stimulus evoked Compound Action Potential (CAP) is sustained for up to 30 minutes, and thereafter rapidly falls to zero. Optic nerve glycogen decreases during aglycemia and is exhausted after about 30 minutes. This temporal correlation between glycogen content and maintenance of the CAP suggests that in the face of aglycemia, glycogen supports conduction, but once the limited glycogen stores are exhausted the CAP fails. The glycogen is metabolised to lactate, which is shuttled from the astrocyte to the axon to serve as a transportable energy substrate. In the peripheral nervous system a similar scheme occurs in which Schwann cell glycogen supports conduction of large myelinated A fibres during aglycemia via. transfer of the glycogen-derived conduit lactate. The smaller unmyelinated C fibres do not benefit from the presence of glycogen. However inhibiting glycogen metabolism with DAB during aglycemia abolishes any benefit the A fibres derive from glycogen, and their latency to failure resembles that of the C fibres.