PLoS biology, 2020-12, Vol.18 (12), p.e3000621-e3000621
2020
Details
- Autor(en) / Beteiligte
- Titel
- Oligodendrocytes support axonal transport and maintenance via exosome secretion
- Ist Teil von
- PLoS biology, 2020-12, Vol.18 (12), p.e3000621-e3000621
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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 oligodendroglial exosome secretion is impaired in 2 mouse mutants exhibiting secondary axonal degeneration due to oligodendrocyte-specific gene defects. Wild-type oligodendroglial exosomes support neurons by improving the metabolic state and promoting axonal transport in nutrient-deprived neurons. Mutant oligodendrocytes release fewer exosomes, which share a common signature of underrepresented proteins. Notably, mutant exosomes lack the ability to support nutrient-deprived neurons and to promote axonal transport. Together, these findings indicate that glia-to-neuron exosome transfer promotes neuronal long-term maintenance by facilitating axonal transport, providing a novel mechanistic link between myelin diseases and secondary loss of axonal integrity.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1545-7885, 1544-9173eISSN: 1545-7885DOI: 10.1371/journal.pbio.3000621Titel-ID: cdi_plos_journals_2479139615
- Format
- –
- Schlagworte
- Animals, Axonal transport, Axonal Transport - genetics, Axonal Transport - physiology, Axons, Axons - physiology, Biology and Life Sciences, Brain-derived neurotrophic factor, Centrifugation, Chromatography, Differential thermal analysis, Exosomes, Exosomes - metabolism, Exosomes - physiology, Extracellular Vesicles - metabolism, Extracellular Vesicles - physiology, Female, Glycoproteins, HEK293 Cells, Hippocampus, Homeostasis, Humans, Incubation, Maintenance, Male, Medicine and Health Sciences, Metabolism, Metabolites, Mice, Mice, Inbred C57BL, Myelin, Myelin proteolipid protein, Myelin Sheath - metabolism, Myelin-associated glycoprotein, Neurodegeneration, Neuroglia, Neurons, Neurons - metabolism, Neurons - physiology, Oligodendrocytes, Oligodendroglia - metabolism, Oligodendroglia - physiology, Oxidative stress, Physical Sciences, Pretreatment, Proteins, Proteolipid protein, Protocol (computers), Research and Analysis Methods, Signal Transduction - physiology, Size exclusion chromatography, Transmission electron microscopy, Ultracentrifugation, Vesicles