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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

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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 3

Glial cells provide metabolic support to neurons.

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Glial cells provide metabolic support to neurons.
(i) At the synapse, ne...
(i) At the synapse, neuronal activity releases glutamate (Glu) in the extracellular space, which is taken up by astrocytic GLT-1. Glutamate uptake drives glucose (Glc) uptake through glucose transporters (GLUT1) in astrocytes; glucose is subsequently converted to pyruvate (Pyr) and lactate (Lac). Intracellular lactate can be shuttled to neurons through astrocyte MCT1 and MCT4 and neuronal MCT2. Neuronal lactate can fuel neuronal ATP synthesis in the mitochondria after conversion to pyruvate. (ii) Astrocytes contact neurons at the nodes of Ranvier, and can shuttle metabolic substrates through astrocytic MCT1 and MCT4. Neurons can take up these substrates through MCT2, using them to fuel mitochondrial ATP synthesis. (iii) Oligodendrocyte myelin consists of compacted and uncompacted regions. The latter allow for transport of metabolites within the myelin, toward the adaxonal (nearest to the axon) myelin inner tongue, from where metabolites can be transported to neurons. (iv) Transport occurs through MCT1 expressed at the adaxonal oligodendrocyte process and moves substrates into the periaxonal space, where metabolites can be taken up by neurons through MCT2 and processed for ATP synthesis. (v) The metabolic supportive function of oligodendrocytes is regulated by glutamate binding to the NMDA receptor, followed by enhanced oligodendrocyte glucose uptake and conversion of glucose to lactate, which can then be provided to the neurons. (vi) Another potential source of oligodendrocyte lactate is through gap junction coupling with astrocytes. Whether metabolic supply through this pathway is essential for neuronal metabolic support remains to be determined.

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