Oligodendroglia: metabolic supporters of axons

Abstract

Axons are specialized extensions of neurons that are critical for the organization of the nervous system. In order to maintain function in axons that often extend some distance from the cell body, specialized mechanisms of energy delivery are likely necessary. Over the last 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 will discuss evidence for the vulnerability of neurons to energy deprivation, the importance of oligodendrocytes for axon function and survival, and very recent data suggesting that transfer of energy metabolites from oligodendroglia to axons through monocarboxylate transporter 1 may be critical for the survival of axons. This pathway has important implications both for the basic biology of the nervous system as well as for human neurologic disease. New insights into the role of oligodendroglial biology provide an exciting opportunity for revisions in nervous system biology, understanding myelin-based disorders and in therapeutics development.

Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

“…Here, we provide direct evidence that oligodendrocyte-astrocyte gap junctions are also permeable to the fluorescent glucose analog 2-NBDG. Considering the capacity of astrocytes to uptake, store and supply energy substrates (Rouach et al, 2008), it is likely that glucose and/or its metabolites might be transferred from astrocytes to oligodendrocytes through oligodendrocyte-astrocyte gap junctions as recently hypothesized (Morrison et al, 2013). In this regard, our findings might provide a new understanding of a connexin-channel- Fig.…”

“…Here, we provide evidence demonstrating that a glucose analog cannot exchange between OPCs and astrocytes due to the absence of gap junction, whereas hemichannel activity supports glucose uptake in OPCs, which is essential for their proliferation. In addition, for the first time, we show that a glucose analog can be transferred through oligodendrocyte-astrocyte gap junctions, which provides the basis for a panglial metabolic route that previously had only been suggested but not demonstrated (Morrison et al, 2013). During brain development, oligodendroglial-specific Cx47 and Cx32 are detected at embryonic stages, whereas Cx29 appears at P0.…”

“…It is well known that astrocytes are the major energy source for neurons because they take up glucose through Gluts and provide the metabolite lactate for neurons through the 'MCT-mediated astrocyte neuron lactate shuttle' Magistretti, 1994, 2012). Similarly, oligodendrocytes can absorb extracellular glucose and/or lactate through Glut1 (also known as SLC2A1) and MCT1, respectively (Hirrlinger and Nave, 2014;Morrison et al, 2013;Rinholm et al, 2011;Saab et al, 2013). By contrast, OPCs do not express MCT1 (Lee et al, 2012), and there is a lack of evidence showing the expression of other Gluts in OPCs.…”

“…At a more integrated level, the astroglial networking mediated by gap junctions sustains neuronal activity through the intercellular trafficking of metabolites (Rouach et al, 2008). Based on these findings, it has been hypothesized that gap junction communication between astrocytes and oligodendrocytes might allow oligodendrocytes to obtain energy supplies from astrocytes (Hirrlinger and Nave, 2014;Morrison et al, 2013). However, it is not clear whether this gapjunction-mediated energy substrate pathway also exists between OPCs and astrocytes.…”

Delivery on call: exosomes as “care packages” from glial cells for stressed neurons

“…After myelination, oligodendrocytes obtain their energy mainly from glycolysis and may provide glycolytic substrates such as lactate to energy-demanding axons [8]. In addition, axonal maintenance possibly requires the transfer of oligodendroglial exosomes to axons [4,7].…”