Oligodendroglia: metabolic supporters of neurons
Thomas Philips, Jeffrey D. Rothstein
Thomas Philips, Jeffrey D. Rothstein
Published September 1, 2017
Citation Information: J Clin Invest. 2017;127(9):3271-3280. https://doi.org/10.1172/JCI90610.
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Review Series

Oligodendroglia: metabolic supporters of neurons

Abstract

Oligodendrocytes are glial cells that populate the entire CNS after they have differentiated from oligodendrocyte progenitor cells. From birth onward, oligodendrocytes initiate wrapping of neuronal axons with a multilamellar lipid structure called myelin. Apart from their well-established function in action potential propagation, more recent data indicate that oligodendrocytes are essential for providing metabolic support to neurons. Oligodendrocytes transfer energy metabolites to neurons through cytoplasmic “myelinic” channels and monocarboxylate transporters, which allow for the fast delivery of short-carbon-chain energy metabolites like pyruvate and lactate to neurons. These substrates are metabolized and contribute to ATP synthesis in neurons. This Review will discuss our current understanding of this metabolic supportive function of oligodendrocytes and its potential impact in human neurodegenerative disease and related animal models.

Authors

Thomas Philips, Jeffrey D. Rothstein

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Figure 2

Oligodendrocytes provide metabolic support to neurons.

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Oligodendrocytes provide metabolic support to neurons. (A) Normal myelin...
(A) Normal myelin with compacted (dark blue) and uncompacted (light blue) channels form a multilamellar structure around the axon. (B) In PLP-null animals, myelin appears to be ultrastructurally normal, but the underlying axons show signs of degeneration. (C) In MBP-null mice (shiverer mice), only a thin sheath of uncompacted myelin wraps the axon. Despite this dysmyelination, these mice develop normally and axons are intact. (D) The myelin in CNPase-null mice is more compacted than normal as a result of the loss of the uncompacted myelinic channels, resulting in severe axonal degeneration. (E) Loss of MCT1 in oligodendrocytes leads to axonal degeneration despite normal-appearing myelin wrapping the axons. All these models show a clear distinction between the ability of myelin to support axonal conductance and its ability to provide trophic support to the axon. How myelinic channels are affected in the PLP- and MCT1-null mice remains to be elucidated.