Oligodendrocytes support axonal transport and maintenance via exosome secretion

Frühbeis, Carsten; Kuo-Elsner, Wen Ping; Müller, Christina; Barth, Kerstin; Peris, Leticia; Tenzer, Stefan; Möbius, Wiebke; Werner, Hauke; Nave, Klaus‐Armin; Fröhlich, Dominik; Krämer-Albers, Eva-Maria

doi:10.1371/journal.pbio.3000621

Cited by 102 publications

(87 citation statements)

References 60 publications

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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%

Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons

Duncan

Simkins

Emery

2021

Front. Cell Dev. Biol.

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The myelination of axons by oligodendrocytes is a highly complex cell-to-cell interaction. Oligodendrocytes and axons have a reciprocal signaling relationship in which oligodendrocytes receive cues from axons that direct their myelination, and oligodendrocytes subsequently shape axonal structure and conduction. Oligodendrocytes are necessary for the maturation of excitatory domains on the axon including nodes of Ranvier, help buffer potassium, and support neuronal energy metabolism. Disruption of the oligodendrocyte-axon unit in traumatic injuries, Alzheimer’s disease and demyelinating diseases such as multiple sclerosis results in axonal dysfunction and can culminate in neurodegeneration. In this review, we discuss the mechanisms by which demyelination and loss of oligodendrocytes compromise axons. We highlight the intra-axonal cascades initiated by demyelination that can result in irreversible axonal damage. Both the restoration of oligodendrocyte myelination or neuroprotective therapies targeting these intra-axonal cascades are likely to have therapeutic potential in disorders in which oligodendrocyte support of axons is disrupted.

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Section: Long-term Breakdown Of Oligodendrocyte Support In Myelin Genmentioning

confidence: 99%

Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons

Duncan

Simkins

Emery

2021

Front. Cell Dev. Biol.

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“…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%

Extracellular Vesicles in neural cell interaction and CNS homeostasis

et al. 2021

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Central nervous system (CNS) homeostasis critically depends on the interaction between neurons and glia cells. Extracellular vesicles (EVs) recently emerged as versatile messengers in CNS cell communication. EVs are released by neurons and glia in activity-dependent manner and address multiple target cells within and outside the nervous system. Here, we summarize the recent advances in understanding the physiological roles of EVs in the nervous system and their ability to deliver signals across the CNS barriers. In addition to the disposal of cellular components via EVs and clearance by phagocytic cells, EVs are involved in plasticity-associated processes, mediate trophic support and neuroprotection, promote axonal maintenance, and modulate neuroinflammation. While individual functional components of the EV cargo are becoming progressively identified, the role of neural EVs as compound multimodal signaling entities remains to be elucidated. Novel transgenic models and imaging technologies allow EVtracking in vivo and provide further insight into EV targeting and their mode of action. Overall, EVs represent key players in the maintenance of CNS homeostasis essential for the life-long performance of neural networks and thus provide a wide spectrum of biomedical applications.

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“…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%

Oligodendroglial Energy Metabolism and (re)Myelination

Tepavčević

2021

Life

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Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has been evoked as an important contributor to various CNS disorders, including multiple sclerosis (MS). Thus, dysregulation of energy homeostasis in oligodendroglia may be an important contributor to myelin dysfunction and lack of repair observed in the disease. This article will focus on energy metabolism pathways in oligodendroglial cells and highlight differences dependent on the maturation stage of the cell. In addition, it will emphasize that the use of alternative energy sources by oligodendroglia may be required to save glucose for functions that cannot be fulfilled by other metabolites, thus ensuring sufficient energy input for both myelin synthesis and trophic support to the axons. Finally, it will point out that neuropathological findings in a subtype of MS lesions likely reflect defective oligodendroglial energy homeostasis in the disease.

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Oligodendrocytes support axonal transport and maintenance via exosome secretion

Cited by 102 publications

References 60 publications

Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons

Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons

Extracellular Vesicles in neural cell interaction and CNS homeostasis

Oligodendroglial Energy Metabolism and (re)Myelination

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