title: Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication.
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.
authors.affiliation: Department of Molecular Cell Biology, University of Mainz, Mainz, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Frühbeis
authors.forename: Dominik
authors.initials: D
authors.lastname: Fröhlich
authors.forename: Wen Ping
authors.initials: WP
authors.lastname: Kuo
authors.forename: Jesa
authors.initials: J
authors.lastname: Amphornrat
authors.forename: Sebastian
authors.initials: S
authors.lastname: Thilemann
authors.forename: Aiman S
authors.initials: AS
authors.lastname: Saab
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.forename: Wiebke
authors.initials: W
authors.lastname: Möbius
authors.forename: Sandra
authors.initials: S
authors.lastname: Goebbels
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
authors.forename: Anja
authors.initials: A
authors.lastname: Schneider
authors.forename: Mikael
authors.initials: M
authors.lastname: Simons
authors.forename: Matthias
authors.initials: M
authors.lastname: Klugmann
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Trotter
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Krämer-Albers
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055354:Exosomes / Q000187:drug effects*; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018377:Neurotransmitter Agents; D018698:Glutamic Acid