2020
DOI: 10.1371/journal.pbio.3000621
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Oligodendrocytes support axonal transport and maintenance via exosome secretion

Abstract: Neurons extend long axons that require maintenance and are susceptible to degeneration. Long-term integrity of axons depends on intrinsic mechanisms including axonal transport and extrinsic support from adjacent glial cells. The mechanisms of support provided by myelinating oligodendrocytes to underlying axons are only partly understood. Oligodendrocytes release extracellular vesicles (EVs) with properties of exosomes, which upon delivery to neurons improve neuronal viability in vitro. Here, we show that oligo… Show more

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Cited by 102 publications
(86 citation statements)
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References 60 publications
(70 reference statements)
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“…Likewise, CNP is known to maintain the opening of cytoplasmic channels in myelin (Snaidero et al, 2017). If these channels are compromised in the Cnp1 null mice, oligodendrocyte support functions such as delivery of EVs (Fruhbeis et al, 2020) or lactate (Funfschilling et al, 2012;Lee et al, 2012) could be disrupted, leaving the myelinated portions of the axons stressed and vulnerable to loss. These studies indicate that, a long-term breakdown of normal oligodendroglial support, even if the myelin sheath is broadly maintained, can trigger axon loss.…”
Section: Long-term Breakdown Of Oligodendrocyte Support In Myelin Genmentioning
confidence: 99%
“…Likewise, CNP is known to maintain the opening of cytoplasmic channels in myelin (Snaidero et al, 2017). If these channels are compromised in the Cnp1 null mice, oligodendrocyte support functions such as delivery of EVs (Fruhbeis et al, 2020) or lactate (Funfschilling et al, 2012;Lee et al, 2012) could be disrupted, leaving the myelinated portions of the axons stressed and vulnerable to loss. These studies indicate that, a long-term breakdown of normal oligodendroglial support, even if the myelin sheath is broadly maintained, can trigger axon loss.…”
Section: Long-term Breakdown Of Oligodendrocyte Support In Myelin Genmentioning
confidence: 99%
“…Mature myelinating oligodendrocytes release EVs from MVBs upon stimulation with the neurotransmitter glutamate. Neurons that internalize these EVs are more robust toward various stress conditions and are able to sustain a high level of metabolic activity as well as axonal transport 17,53 (Figure 1E). Intriguingly, mice with secondary axonal degeneration due to the lack of the glial proteins PLP and CNP exhibit impaired oligodendroglial EV release and have lost the ability to promote axonal transport 53 .…”
Section: Cellular Routes Of Neural Evsmentioning
confidence: 99%
“…Neurons that internalize these EVs are more robust toward various stress conditions and are able to sustain a high level of metabolic activity as well as axonal transport 17,53 (Figure 1E). Intriguingly, mice with secondary axonal degeneration due to the lack of the glial proteins PLP and CNP exhibit impaired oligodendroglial EV release and have lost the ability to promote axonal transport 53 . EV transfer from oligodendrocytes to neurons may thus provide a means of support, essential for long‐term neuronal survival and axonal maintenance.…”
Section: Cellular Routes Of Neural Evsmentioning
confidence: 99%
“…Axonal trophic support by oligodendrocytes may also be carried out via myelin peroxisomes, potentially by fatty acid transfer for beta oxidation in the axons [51]. Recently, it has also been shown that oligodendrocytes support axonal transport and maintain the health of nutrient-deprived axons in vitro via exosomes [52].…”
Section: Figurementioning
confidence: 99%