Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism

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

Research output: Contribution to journalArticlepeer-review

181 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)119-132
Number of pages14
JournalNeuron
Volume91
Issue number1
DOIs
StatePublished - Jul 6 2016
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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