Oligodendroglia: metabolic supporters of axons

Abstract

Axons are specialized extensions of neurons that are critical for the organization of the nervous system. To maintain function in axons that often extend some distance from the cell body, specialized mechanisms of energy delivery are likely to be necessary. Over the past decade, greater understanding of human demyelinating diseases and the development of animal models have suggested that oligodendroglia are critical for maintaining the function of axons. In this review, we discuss evidence for the vulnerability of neurons to energy deprivation, the importance of oligodendrocytes for axon function and survival, and recent data suggesting that transfer of energy metabolites from oligodendroglia to axons through monocarboxylate transporter 1 (MCT1) may be critical for the survival of axons. This pathway has important implications both for the basic biology of the nervous system and for human neurological disease. New insights into the role of oligodendroglial biology provide an exciting opportunity for revisions in nervous system biology, understanding myelin-based disorders, and therapeutics development.

Keywords: ALS; MCT1; lactate; myelin; neurodegeneration; oligodendroglia.

Figure 1

Multiple manipulations that attenuate MCT1 in rodent models (A–D) or spinal cord organotypic cultures (E,F) produce motor neuron cell death (A,F; arrows indicate motor neurons), spinal neuron cell death (E; propidium iodide) or axon injury (B–D).

Figure 2

Schematic of oligodendroglia and axonal monocarboxylate transporters. Oligodendroglia transport lactate, or other monocarboxylates, to the periaxonal space through MCT1. From this space, lactate can be taken up into axons by MCT2, converted to pyruvate by lactate dehydrogenase, and imported into mitochondria for oxidative phosphorylation and the subsequent generation of ATP.

Figure 3

Astrocytes and oligodendroglia form a syncitium connected together by gap junctions formed by specific connexin molecules. Though just a hypothesis, lactate may transport from astrocytes to oligodendroglia through gap junctions prior to being used as axonal energy.