Oligodendroglial NMDA receptors regulate glucose import and axonal energy 
metabolism

Saab, Aiman S.; Tzvetanova, Iva D.; Trevisiol, Andrea; Baltan, Selva; Dibaj, Payam; Kusch, Kathrin; Möbius, Wiebke; Goetze, Bianka; Jahn, Hannah M.; Huang, Wenhui; Steffens, Heinz; Schomburg, Eike D.; Pérez-Samartín, Alberto; Pérez-Cerdá, Fernando; Bakhtiari, Davood; Matute, Carlos; Löwel, Siegrid; Griesinger, Christian; Hirrlinger, Johannes; Kirchhoff, Frank; Nave, Klaus-Armin

doi:10.1016/j.neuron.2016.05.016

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Oligodendroglial NMDA receptors regulate glucose import and axonal energy metabolism

MPS-Authors

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Saab, Aiman S.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182459

Tzvetanova, Iva D.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182611

Trevisiol, Andrea
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182129

Dibaj, Payam
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182268

Kusch, Kathrin
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182306

Möbius, Wiebke
Electron microscopy, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons194838

Jahn, Hannah M.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons196716

Huang, Wenhui
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182201

Hirrlinger, Johannes
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182243

Kirchhoff, Frank
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182320

Nave, Klaus-Armin
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Citation

Saab, A. S., Tzvetanova, I. D., Trevisiol, A., Baltan, S., Dibaj, P., Kusch, K., et al. (2016). Oligodendroglial NMDA receptors regulate glucose import and axonal energy metabolism. Neuron, 91(1), 119-132. doi:10.1016/j.neuron.2016.05.016.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002C-1055-5

Abstract

Oligodendrocytes make myelin and support axons metabolically with lactate. However, it is unknown how glucose utilization and glycolysis are adapted to the different axonal energy demands. Spiking axons release glutamate and oligodendrocytes express NMDA receptors of unknown function. Here we show that the stimulation of oligodendroglial NMDA receptors mobilizes glucose transporter GLUT1, leading to its incorporation into the myelin compartment in vivo. When myelinated optic nerves from conditional NMDA receptor mutants are challenged with transient oxygen-glucose deprivation, they show a reduced functional recovery when returned to oxygen-glucose but are indistinguishable from wild-type when provided with oxygen-lactate. Moreover, the functional integrity of isolated optic nerves, which are electrically silent, is extended by preincubation with NMDA, mimicking axonal activity, and shortened by NMDA receptor blockers. This reveals a novel aspect of neuronal energy metabolism in which activity-dependent glutamate release enhances oligodendroglial glucose uptake and glycolytic support of fast spiking axons.