The role of oligodendroglial exosome secretion in axon-glia communication, glial support, and maintenance of axonal integrity

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Oligodendrocytes build the central nervous system myelin sheath and in addition provide trophic support to neurons responsible for long-term axonal maintenance (glial support). Loss of glial support results in progressive degeneration of axons and accounts for the irreversible course of many myelin diseases. We have discovered that oligodendrocytes release extracellular vesicles termed exosomes, which have the ability to deliver biologically functional molecules to neurons and confer stress protection. In this project we will elucidate the role of exosomes in neuron-glia communication and glial support. We will study the functional impact of oligodendrocyte-neuron exosome transfer in vitro and in vivo utilizing transgenic mouse models. The role of micro-RNAs enriched in exosomes in horizontal regulation of neuronal target genes will be investigated. Our goal is to explore the molecular mechanisms that exosomes employ to facilitate axonal maintenance and sustain their integrity. This study will help to define target molecules that may be therapeutically addressed to prevent axon loss in myelin diseases as well other neurodegenerative diseases.