Oligodendrocytes in the Mouse Corpus Callosum Maintain Axonal Function by Delivery of Glucose

Niklas Meyer,Nadine Richter,Zoya Fan,Gabrielle Siemonsmeier,Tatyana Pivneva,Philipp Jordan,Christian Steinhäuser,Marcus Semtner,Christiane Nolte,Helmut Kettenmann

doi:10.1016/j.celrep.2018.02.022

Abstract

In the optic nerve, oligodendrocytes maintain axonal function by supplying lactate as an energy substrate. Here, we report that, in acute brain slices of the mouse corpus callosum, exogenous glucose deprivation (EGD) abolished compound action potentials (CAPs), which neither lactate nor pyruvate could prevent. Loading an oligodendrocyte with 20mM glucose using a patch pipette prevented EGD-mediated CAP reduction in about 70% of experiments. Loading oligodendrocytes with lactate rescued CAPs less efficiently than glucose. In mice lacking connexin 47, oligodendrocyte filling with glucose did not prevent CAP loss, emphasizing the importance of glial networks for axonal energy supply. Compared with the optic nerve, the astrocyte network in the corpus callosum was less dense, and loading astrocytes with glucose did not prevent CAP loss during EGD. We suggest that callosal oligodendrocyte networks provide energy to sustain axonal function predominantly by glucose delivery, and mechanisms of metabolic support vary across different white matter regions.

Highlights

In white matter, oligodendrocytes are instrumental to fuel axonal activity, and the optic nerve has served as a convenient model to study the mechanism of this cellular interaction (Morrison et al, 2013)
Loading oligodendrocytes with lactate rescued compound action potentials (CAPs) less efficiently than glucose
We suggest that callosal oligodendrocyte networks provide energy to sustain axonal function predominantly by glucose delivery, and mechanisms of metabolic support vary across different white matter regions

Summary

Introduction

Oligodendrocytes are instrumental to fuel axonal activity, and the optic nerve has served as a convenient model to study the mechanism of this cellular interaction (Morrison et al, 2013). Compound action potentials (CAPs) can be evoked in acutely isolated optic nerve preparations and can persist for several hours but rapidly fail under aglycemic conditions This failure can be effectively prevented by perfusion of L-lactate (Brown et al, 2003). NMDA receptor activation in response to glutamate release increases trafficking of glucose transporter GLUT1 to the oligodendrocyte membrane, sustaining glucose import to oligodendrocytes for glycolysis and downstream transfer of lactate to axons. This mechanism might be important in diseases linked to energy deprivation (e.g., white matter ischemia)

Results

Discussion

Conclusion