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  • br Myelin and metabolism In addition

    2021-11-22


    Myelin and metabolism In addition to promoting efficient pyk2 inhibitor propagation, myelin is also critical for trophic and metabolic support of axons [56]. To provide metabolites to axons accurately, glia must ‘know’ the metabolic requirements of axons. Could electrical activity by axons function as a means of communication? NMDA glutamate receptors are present on oligodendrocytes [57, 58], but were thought to be dispensable for oligodendrocyte development, myelination, and injury response [59, 60]. However, recent work has implicated these receptors in mediating calcium influxes in mature oligodendrocytes [61]. Furthermore, NMDA receptors have been shown to link electrical activity in axons to the production of lactate by oligodendrocytes, a critical energy source for axons. By ‘learning’ via NMDA receptor signaling which axons are fast spiking, oligodendrocytes are able to vary lactate production. Loss of NMDA receptors specifically in oligodendrocytes, while not critical during development, causes eventual neurodegeneration from reduced metabolism []. Lactate production and metabolic support of axons by SCs is also critical in the PNS [63, 64]. The lactate transporter that is used by oligodendrocytes, MCT1, is present in SCs and mediates axonal health [65, 66]. However, these studies did not address a role for electrical activity in SC regulation of axonal metabolism. Interestingly, a recent report found that ATP release by electrically active axons mediates mitochondrial signaling to promote energy production in SCs and disruption of this signaling pathway resulted in hypomyelination [67].
    Conclusion and outlook From static insulating factor to dynamic structure critical in enabling nervous system plasticity, our conceptions about myelin have changed dramatically in recent years. However, although both SCs and oligodendrocytes produce myelin, the mechanisms by which they do so are distinct (Figure 3). Oligodendrocytes possess an intrinsic ability to myelinate that is fine-tuned by environmental cues, such as mechanical stimulation and electrical activity from axons. New studies suggest the existence of distinct subsets of oligodendrocytes, raising the possibility that such heterogeneity could contribute to differences in innate myelination and re-myelination abilities. It will be exciting to uncover the extent to which interplay between the extracellular environment and oligodendrocyte heterogeneity influences myelination during development and repair. Advances in cellular techniques, including 3D electron microscopic reconstructions and live imaging, have contributed to a better understanding of the physical process of myelination by oligodendrocytes, including a surprising role for actin dynamics. Further research into the cytoskeletal and architectural reorganization of membrane during myelination will help us better understand this feat of morphogenesis and elucidate how to promote re-myelination in disease or injury. SCs are incapable of myelinating inert structures [37], relying instead on instructive cues. PNS myelination also appears to be less finely tuned compared to the CNS, with stricter correlations between axon diameter and myelin thickness. Whether PNS myelin undergoes dynamic changes similar to CNS myelin has not been well studied. While early work demonstrated a role for axonal activity in modulating SC development and myelination [68], this area of research has lagged behind progress made in the CNS. The mechanisms by which SCs elaborate a myelin sheath are similarly mysterious. One pertinent question is whether actin dynamics, which are vital during CNS myelination, play an analogous role in SCs. A current focus in SCs is on mechanotransduction, and advances in this area are already guiding therapeutic developments through techniques such as optimal matrices for acellular nerve allografts [69].
    Conflict of interest statement