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      Extracellular vesicles as mediators of neuron-glia communication

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          Abstract

          In the nervous system, glia cells maintain homeostasis, synthesize myelin, provide metabolic support, and participate in immune defense. The communication between glia and neurons is essential to synchronize these diverse functions with brain activity. Evidence is accumulating that secreted extracellular vesicles (EVs), such as exosomes and shedding microvesicles, are key players in intercellular signaling. The cells of the nervous system secrete EVs, which potentially carry protein and RNA cargo from one cell to another. After delivery, the cargo has the ability to modify the target cell phenotype. Here, we review the recent advances in understanding the role of EV secretion by astrocytes, microglia, and oligodendrocytes in the central nervous system. Current work has demonstrated that oligodendrocytes transfer exosomes to neurons as a result of neurotransmitter signaling suggesting that these vesicles may mediate glial support of neurons.

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          Most cited references30

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          Exosome secretion: molecular mechanisms and roles in immune responses.

          Exosomes are small membrane vesicles, secreted by most cell types from multivesicular endosomes, and thought to play important roles in intercellular communications. Initially described in 1983, as specifically secreted by reticulocytes, exosomes became of interest for immunologists in 1996, when they were proposed to play a role in antigen presentation. More recently, the finding that exosomes carry genetic materials, mRNA and miRNA, has been a major breakthrough in the field, unveiling their capacity to vehicle genetic messages. It is now clear that not only immune cells but probably all cell types are able to secrete exosomes: their range of possible functions expands well beyond immunology to neurobiology, stem cell and tumor biology, and their use in clinical applications as biomarkers or as therapeutic tools is an extensive area of research. Despite intensive efforts to understand their functions, two issues remain to be solved in the future: (i) what are the physiological function(s) of exosomes in vivo and (ii) what are the relative contributions of exosomes and of other secreted membrane vesicles in these proposed functions? Here, we will focus on the current ideas on exosomes and immune responses, but also on their mechanisms of secretion and the use of this knowledge to elucidate the latter issue. © 2011 John Wiley & Sons A/S.
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            Exosomes: secreted vesicles and intercellular communications

            Exosomes are small membrane vesicles of endocytic origin secreted by most cell types, and are thought to play important roles in intercellular communications. Although exosomes were originally described in 1983, interest in these vesicles has really increased dramatically in the last 3 years, after the finding that they contain mRNA and microRNA. This discovery sparked renewed interest for the general field of membrane vesicles involved in intercellular communications, and research on these structures has grown exponentially over the last few years, probing their composition and function, as well as their potential value as biomarkers.
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              Myelination and support of axonal integrity by glia.

              The myelination of axons by glial cells was the last major step in the evolution of cells in the vertebrate nervous system, and white-matter tracts are key to the architecture of the mammalian brain. Cell biology and mouse genetics have provided insight into axon-glia signalling and the molecular architecture of the myelin sheath. Glial cells that myelinate axons were found to have a dual role by also supporting the long-term integrity of those axons. This function may be independent of myelin itself. Myelin abnormalities cause a number of neurological diseases, and may also contribute to complex neuropsychiatric disorders.
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                Author and article information

                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                30 October 2013
                2013
                : 7
                : 182
                Affiliations
                Department of Molecular Cell Biology, Johannes Gutenberg University Mainz Mainz, Germany
                Author notes

                Edited by: Martin Stangel, Hannover Medical School, Germany

                Reviewed by: Claudia Verderio, Consiglio Nazionale delle Ricerche, Italy; Valentina Bonetto, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto di Ricerche Farmacologiche Mario Negri, Italy

                *Correspondence: Carsten Frühbeis, Department of Molecular Cell Biology, Johannes Gutenberg University Mainz, Bentzelweg 3, 55128 Mainz, Germany email: fruehbei@uni-mainz.de

                This article was submitted to the journal Frontiers in Cellular Neuroscience.

                Article
                10.3389/fncel.2013.00182
                3812991
                24194697
                a29320f8-7f91-4163-9e9b-f47e390a9156
                Copyright © 2013 Frühbeis, Fröhlich, Kuo and Krämer-Albers.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 13 September 2013
                : 01 October 2013
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 65, Pages: 6, Words: 0
                Categories
                Neuroscience
                Mini Review Article

                Neurosciences
                extracellular vesicles,exosomes,neuron–glia communication,oligodendrocytes,microglia,astrocytes,neuroprotection

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