Journal Article

Fructose Metabolism in the Adult Mouse Optic Nerve, A Central White Matter Tract

Ray, David E, Fowler, Maxine J, Rathbone, Alex J, Ransom, Bruce R, Allen, Lynne M, Brown, Angus M, Meakin, Paul J

2007

Overview

Our recent report that fructose supported the metabolism of some, but not all axons, in the adult mouse optic nerve prompted us to investigate in detail fructose metabolism in this tissue, a typical central white matter tract, as these data imply efficient fructose metabolism in the central nervous system (CNS). In artificial cerebrospinal fluid containing 10 mmol/L glucose or 20 mmol/L fructose, the stimulus-evoked compound action potential (CAP) recorded from the optic nerve consisted of three stable peaks. Replacing 10 mmol/L glucose with 10 mmol/L fructose, however, caused delayed loss of the 1st CAP peak (the 2nd and 3rd CAP peaks were unaffected). Glycogen-derived metabolic substrate(s) temporarily sustained the 1st CAP peak in 10 mmol/L fructose, as depletion of tissue glycogen by a prior period of aglycaemia or high-frequency CAP discharge rendered fructose incapable of supporting the 1st CAP peak. Enzyme assays showed the presence of both hexokinase and fructokinase (both of which can phosphorylate fructose) in the optic nerve. In contrast, only hexokinase was expressed in cerebral cortex. Hexokinase in optic nerve had low affinity and low capacity with fructose as substrate, whereas fructokinase displayed high affinity and high capacity for fructose. These findings suggest an explanation for the curious fact that the fast conducting axons comprising the 1st peak of the CAP are not supported in 10 mmol/L fructose medium; these axons probably do not express fructokinase, a requirement for efficient fructose metabolism.

• Publisher: SAGE Publications,Lippincott Williams & Wilkins,Sage Publications Ltd
• Subject: Action Potentials - physiology / Algorithms / Animals / Axons - metabolism / Biological and medical sciences / Biological Transport, Active - physiology / Blotting, Western / Data Interpretation, Statistical / Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes / Energy Metabolism - physiology / Fructokinases - metabolism / Fructose - metabolism / Glycogen - physiology / Hexokinase - metabolism / Immunohistochemistry / Male / Medical sciences / Mice / Nervous system (semeiology, syndromes) / Neurology / Neuropharmacology / Neuroprotective agent / Optic Nerve - enzymology / Optic Nerve - metabolism / Pharmacology. Drug treatments / Vascular diseases and vascular malformations of the nervous system