Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication

PLoS Biol. 2013 Jul;11(7):e1001604. doi: 10.1371/journal.pbio.1001604. Epub 2013 Jul 9.

Abstract

Reciprocal interactions between neurons and oligodendrocytes are not only crucial for myelination, but also for long-term survival of axons. Degeneration of axons occurs in several human myelin diseases, however the molecular mechanisms of axon-glia communication maintaining axon integrity are poorly understood. Here, we describe the signal-mediated transfer of exosomes from oligodendrocytes to neurons. These endosome-derived vesicles are secreted by oligodendrocytes and carry specific protein and RNA cargo. We show that activity-dependent release of the neurotransmitter glutamate triggers oligodendroglial exosome secretion mediated by Ca²⁺ entry through oligodendroglial NMDA and AMPA receptors. In turn, neurons internalize the released exosomes by endocytosis. Injection of oligodendroglia-derived exosomes into the mouse brain results in functional retrieval of exosome cargo in neurons. Supply of cultured neurons with oligodendroglial exosomes improves neuronal viability under conditions of cell stress. These findings indicate that oligodendroglial exosomes participate in a novel mode of bidirectional neuron-glia communication contributing to neuronal integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication / drug effects
  • Cell Survival / drug effects
  • Exosomes / drug effects*
  • Female
  • Glutamic Acid / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurotransmitter Agents / pharmacology*
  • Oligodendroglia / cytology*
  • Oligodendroglia / drug effects
  • Signal Transduction / drug effects

Substances

  • Neurotransmitter Agents
  • Glutamic Acid

Grant support

The study was supported by grants of ELA (2007-027C1) and DFG (KR 3668/1-1) to EMKA, DFG SFB 894 (A12) to FK, DFG Research Center Molecular Physiology of the Brain (CNMPB), and ERC Advanced Grant to KAN. CF received internal research funding for early career researchers from JGU Mainz. MK is an Australian Research Council (ARC) Future Fellow. DF received fellowships from the Stipendienstiftung Rheinland Pfalz and the DFG GRK 1044. WPK is a fellow of the Focus Program Translational Neuroscience JGU Mainz. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.