Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA268

Poster Communications

Sciatic nerve C fibres utilise fructose directly to support conduction whereas A fibre conduction is maintained by Schwann cell fructose-derived lactate

L. R. Rich1, A. M. Brown1

1. School of Life Sciences, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom.

The ability of fructose to support conduction in the mouse sciatic nerve was investigated for the following reasons: (1) Schwann cells can produce fructose from glucose via the polyol pathway (Champe & Harvey, 2008), which may act as an endogenously created metabolic substrate, (2) in the optic nerve there exist differences between fibre subtypes to effectively use fructose as an energy substrate (Meakin et al. 2007), and (3) in the hippocampus, fructose is supplied to neurons by glial cells in the form of a monocarboxylate e.g. lactate (Izumi & Zorumski, 2009), an intriguing parallel with the ability of Schwann cell glycogen-derived lactate to selectively support A fibres (Brown et al. 2012). All procedures were carried out in accordance with the Animals (Scientific Procedures) Act 1986 under appropriate authority of establishment, project and personal licenses. Adult male CD-1 mice were killed by cervical dislocation and decapitated. Sciatic nerves were dissected, placed in a perfusion chamber, superfused with aerated control aCSF containing 10mM glucose. The stimulus evoked compound action potential (CAP) for A and C fibres were evoked with supra-maximal stimuli (Rich and Brown, 2018). The ability of the A and C fibre CAPs to recover in the presence of fructose after aglycaemic exposure was assessed. 20mM fructose restored conduction of both A and C fibres, but the onset of A fibre CAP recovery was delayed compared to equivalent experiments with 10mM glucose. C fibre recovery, however, was identical in 10mM glucose or 20mM fructose. To investigate the role of lactate in the utilisation of fructose by the sciatic nerve we carried out recovery experiments in the presence of cinnemate (200µM) to block axonal uptake of lactate. Cinnemate rendered 20mM fructose unable to restore the A fibre CAP but had no detrimental effect on C fibre CAP recovery with either glucose or fructose. The application of lactate biosensors, to measure lactate release from the nerve ([lac-]o) developed on these findings further. The stable lactate signal recorded in the presence of 20mM fructose increased with the addition of cinnemate and the delayed A fibre CAP recovery in 20mM fructose was temporally correlated with a delayed increase in [lac-]o following reperfusion with 20mM fructose, all of which are consistent with axonal uptake of lactate. It appears that C fibres directly take up and metabolise fructose efficiently whereas A fibre conduction is supported by Schwann cell fructose derived-lactate. Unravelling the metabolic profile of the sciatic nerve and revealing fibre sub-type specific utility of substrates may provide insight into the mechanisms underlying diabetic neuropathy and ultimately help in developing clinically effective neuro-protective strategies.

Where applicable, experiments conform with Society ethical requirements