title: Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal firing rate, signal transduction and gene regulation.
abstract: Exosomes are small membranous vesicles of endocytic origin that are released by almost every cell type. They exert versatile functions in intercellular communication important for many physiological and pathological processes. Recently, exosomes attracted interest with regard to their role in cell-cell communication in the nervous system. We have shown that exosomes released from oligodendrocytes upon stimulation with the neurotransmitter glutamate are internalized by neurons and enhance the neuronal stress tolerance. Here, we demonstrate that oligodendroglial exosomes also promote neuronal survival during oxygen-glucose deprivation, a model of cerebral ischaemia. We show the transfer from oligodendrocytes to neurons of superoxide dismutase and catalase, enzymes which are known to help cells to resist oxidative stress. Additionally, we identify various effects of oligodendroglial exosomes on neuronal physiology. Electrophysiological analysis using in vitro multi-electrode arrays revealed an increased firing rate of neurons exposed to oligodendroglial exosomes. Moreover, gene expression analysis and phosphorylation arrays uncovered differentially expressed genes and altered signal transduction pathways in neurons after exosome treatment. Our study thus provides new insight into the broad spectrum of action of oligodendroglial exosomes and their effects on neuronal physiology. The exchange of extracellular vesicles between neural cells may exhibit remarkable potential to impact brain performance.
authors.affiliation: Molecular Cell Biology, University of Mainz, 55128 Mainz, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Fröhlich
authors.affiliation: Molecular Cell Biology, University of Mainz, 55128 Mainz, Germany Focus Programme Translational Neuroscience, University of Mainz, 55128 Mainz, Germany.
authors.forename: Wen Ping
authors.initials: WP
authors.lastname: Kuo
authors.affiliation: Molecular Cell Biology, University of Mainz, 55128 Mainz, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Frühbeis
authors.affiliation: Institute of Physiology, University Medical Center, 55128 Mainz, Germany Neuro-Electronics Research Flanders, 3001 Leuven, Belgium.
authors.forename: Jyh-Jang
authors.initials: JJ
authors.lastname: Sun
authors.affiliation: Institute of Physiology, University Medical Center, 55128 Mainz, Germany ZIM III, Department of Cardiology, Goethe University Frankfurt, 60389 Frankfurt, Germany.
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Zehendner
authors.affiliation: Focus Programme Translational Neuroscience, University of Mainz, 55128 Mainz, Germany Institute of Physiology, University Medical Center, 55128 Mainz, Germany.
authors.forename: Heiko J
authors.initials: HJ
authors.lastname: Luhmann
authors.affiliation: Division of Developmental Immunology, DKFZ Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Sheena
authors.initials: S
authors.lastname: Pinto
authors.affiliation: Institute of Molecular Biology gGmbH, 55128 Mainz, Germany.
authors.forename: Joern
authors.initials: J
authors.lastname: Toedling
authors.affiliation: Molecular Cell Biology, University of Mainz, 55128 Mainz, Germany Focus Programme Translational Neuroscience, University of Mainz, 55128 Mainz, Germany.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Trotter
authors.affiliation: Molecular Cell Biology, University of Mainz, 55128 Mainz, Germany Focus Programme Translational Neuroscience, University of Mainz, 55128 Mainz, Germany alberse@uni-mainz.de.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Krämer-Albers
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D055354:Exosomes / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D005947:Glucose / Q000172:deficiency; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009474:Neurons / Q000502:physiology*; D009836:Oligodendroglia / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D002374:Catalase; D013482:Superoxide Dismutase; D005947:Glucose
keywords: exosomes; extracellular vesicles; gene regulation; neuron–glia interaction; oligodendrocytes; signal transduction