Oligodendrocytes support axonal transport and maintenance via exosome secretion

PLoS Biol. 2020 Dec 22;18(12):e3000621. doi: 10.1371/journal.pbio.3000621. eCollection 2020 Dec.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axonal Transport / genetics
  • Axonal Transport / physiology*
  • Axons / physiology
  • Exosomes / metabolism
  • Exosomes / physiology
  • Extracellular Vesicles / metabolism
  • Extracellular Vesicles / physiology
  • Female
  • HEK293 Cells
  • Humans
  • Maintenance
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myelin Sheath / metabolism
  • Neuroglia
  • Neurons / metabolism*
  • Neurons / physiology
  • Oligodendroglia / metabolism*
  • Oligodendroglia / physiology
  • Signal Transduction / physiology

Grants and funding

This work was supported by the Deutsche Forschungsgemeinschaft (grants KR 3668/1-1, KR 3668/1-2; https://www.dfg.de/) to EMKA. CF received intramural funding from the Johannes Gutenberg University Mainz (https://www.uni-mainz.de/). WPKE was supported by a PhD-fellowship from the Focus Program Translational Neuroscience, Johannes Gutenberg University Mainz (https://www.blogs.uni-mainz.de/ftn-eng/). CM was supported by a postdoctoral fellowship from the Carl Zeiss Stiftung (https://www.carl-zeiss-stiftung.de/english/index.html). KAN acknowledges research support from the European Research Council (Advanced Grant MyeliNANO; https://erc.europa.eu/) and Adelson Medical Research Foundation (http://www.adelsonfoundation.org/nrrfc.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.