Extracellular vesicles round off communication in the nervous system

The role of extracellular vesicles (EVs) in the nervous system is just beginning to be understood, but has been substantiated both in cell culture and in vivo. Major challenges in this young field include the establishment of a unified nomenclature for EVs and unified methods for their isolation, as well as the transition from studies in cell culture to those documenting their function in healthy and diseased organisms, a feat that is beginning to be achieved in invertebrate models.The release and uptake of EVs in the nervous system by neurons and glial cells provide a novel mechanism of transcellular communication. Indeed, EVs are utilized for the transcellular transport of proteins, enzymes, lipids and RNA, thus influencing the physiology of the receiving cell. Neurons and glia also use EVs as a mechanism to regulate intracellular protein and RNA levels and for protein quality control.Neurons can release EVs both in vivo and in cell culture, and this release is often regulated by depolarization or by agents that increase neuronal excitability. In turn, the release of EVs by glial subpopulations sometimes requires neuronal excitation.Glial cells utilize EVs to regulate differentiation, myelin sheath formation and repair after injury. EVs also serve to propagate inflammatory signals in response to tissue damage and disease.A role for EVs during communication in the nervous system of intact organisms has been demonstrated at the Drosophila melanogaster neuromuscular junction (NMJ) and in Caenorhabditis elegans sensory neurons. At the D. melanogaster NMJ, EVs are used to convey Wnt signals from neurons to muscles, and in C. elegans, such vesicles are used to transmit behaviourally relevant signals between organisms.EVs are emerging as potent participants in the progression of disease, serving as vehicles to spread misfolded proteins in a prion-like fashion, transmitting tumorigenic activity and communicating neuroinflammation. Concomitantly, because of their unique properties, EVs are being explored as shuttles to target therapies.