Saab, Aiman S.

[["dc.bibliographiccitation.firstpage","517"],["dc.bibliographiccitation.issue","7397"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","521"],["dc.bibliographiccitation.volume","485"],["dc.contributor.author","Fünfschilling, Ursula"],["dc.contributor.author","Supplie, Lotti M."],["dc.contributor.author","Mahad, Don"],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Saab, Aiman S."],["dc.contributor.author","Edgar, Julia"],["dc.contributor.author","Brinkmann, Bastian G."],["dc.contributor.author","Kassmann, Celia M."],["dc.contributor.author","Tzvetanova, Iva D."],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Diaz, Francisca"],["dc.contributor.author","Meijer, Dies"],["dc.contributor.author","Suter, Ueli"],["dc.contributor.author","Hamprecht, Bernd"],["dc.contributor.author","Sereda, Michael W."],["dc.contributor.author","Moraes, Carlos T."],["dc.contributor.author","Frahm, Jens"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2017-09-07T11:45:25Z"],["dc.date.available","2017-09-07T11:45:25Z"],["dc.date.issued","2012"],["dc.description.abstract","Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity. However, the underlying support mechanisms are not understood. Here we identify a metabolic component of axon–glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral nervous system, Cox10 conditional mutants exhibit severe neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell death. In the adult central nervous system, we found no signs of demyelination, axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes, which are sensitive to COX inhibitors, post-myelination oligodendrocytes survive well in the absence of COX activity. More importantly, by in vivo magnetic resonance spectroscopy, brain lactate concentrations in mutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics. This indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts. Because myelinated axons can use lactate when energy-deprived, our findings suggest a model in which axon–glia metabolic coupling serves a physiological function."],["dc.identifier.doi","10.1038/nature11007"],["dc.identifier.gro","3150364"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7121"],["dc.language.iso","en"],["dc.notes.status","public"],["dc.relation.issn","0028-0836"],["dc.subject","Neuroscience; Developmental biology; Disease; Cell biology"],["dc.title","Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1001604"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Fruehbeis, Carsten"],["dc.contributor.author","Froehlich, Dominik"],["dc.contributor.author","Kuo, Wen Ping"],["dc.contributor.author","Amphornrat, Jesa"],["dc.contributor.author","Thilemann, Sebastian"],["dc.contributor.author","Saab, Aiman S."],["dc.contributor.author","Kirchhoff, Frank"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Klugmann, Matthias"],["dc.contributor.author","Trotter, Jacqueline"],["dc.contributor.author","Kraemer-Albers, Eva-Maria"],["dc.date.accessioned","2018-11-07T09:22:56Z"],["dc.date.available","2018-11-07T09:22:56Z"],["dc.date.issued","2013"],["dc.description.abstract","Reciprocal interactions between neurons and oligodendrocytes are not only crucial for myelination, but also for long-term survival of axons. Degeneration of axons occurs in several human myelin diseases, however the molecular mechanisms of axon-glia communication maintaining axon integrity are poorly understood. Here, we describe the signal-mediated transfer of exosomes from oligodendrocytes to neurons. These endosome-derived vesicles are secreted by oligodendrocytes and carry specific protein and RNA cargo. We show that activity-dependent release of the neurotransmitter glutamate triggers oligodendroglial exosome secretion mediated by Ca2+ entry through oligodendroglial NMDA and AMPA receptors. In turn, neurons internalize the released exosomes by endocytosis. Injection of oligodendroglia-derived exosomes into the mouse brain results in functional retrieval of exosome cargo in neurons. Supply of cultured neurons with oligodendroglial exosomes improves neuronal viability under conditions of cell stress. These findings indicate that oligodendroglial exosomes participate in a novel mode of bidirectional neuron-glia communication contributing to neuronal integrity."],["dc.identifier.doi","10.1371/journal.pbio.1001604"],["dc.identifier.isi","000322592700008"],["dc.identifier.pmid","23874151"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9144"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29458"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1545-7885"],["dc.rights","CC BY-NC 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/3.0"],["dc.title","Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte-Neuron Communication"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]