Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte–Neuron Communication

Abstract

Author SummaryBrain function largely depends on the communication between electrically excitable neurons and surrounding glial cells. Myelinating oligodendrocytes are a type of brain cell that insulate major neuronal processes (axons) and help to sustainably maintain axonal health, which is poorly understood in molecular terms. Several cell types release microvesicles termed exosomes that include genetic information (primarily RNA) and can act as vehicles transferring specific cargo to target cells. Here, we demonstrate that exosomes secreted by oligodendrocytes in response to neuronal signals enter neurons to make their cargo functionally available to the neuronal metabolism. We revealed in cultured cells that exosome release from oligodendrocytes is triggered by the neurotransmitter glutamate through activation of ionotropic glutamate receptors. We also show that glial exosomes are internalized by neurons via an endocytic pathway. By modifying oligodendroglial exosomes with a reporter enzyme, we could demonstrate that the exosome cargo is recovered by target neurons in culture as well as in vivo after injection of exosomes into the mouse brain. Neurons challenged with stressful growth conditions were protected when treated with oligodendroglial exosomes. The study introduces a new concept of reciprocal cell communication in the nervous system and identifies the signal-mediated transfer of exosomes from oligodendrocytes to neurons contributing to the preservation of axonal health.