Saab, Aiman S.

[["dc.bibliographiccitation.firstpage","119"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.lastpage","132"],["dc.bibliographiccitation.volume","91"],["dc.contributor.author","Saab, Aiman S."],["dc.contributor.author","Tzvetavona, Iva D."],["dc.contributor.author","Trevisiol, Andrea"],["dc.contributor.author","Baltan, Selva"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Goetze, Bianka"],["dc.contributor.author","Jahn, Hannah M."],["dc.contributor.author","Huang, Wenhui"],["dc.contributor.author","Steffens, Heinz"],["dc.contributor.author","Schomburg, Eike D."],["dc.contributor.author","Pérez-Samartín, Alberto"],["dc.contributor.author","Pérez-Cerdá, Fernando"],["dc.contributor.author","Bakhtiari, Davood"],["dc.contributor.author","Matute, Carlos"],["dc.contributor.author","Löwel, Siegrid"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.contributor.author","Kirchhoff, Frank"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2017-09-07T11:44:48Z"],["dc.date.available","2017-09-07T11:44:48Z"],["dc.date.issued","2016"],["dc.description.abstract","Oligodendrocytes make myelin and support axons metabolically with lactate. However, it is unknown how glucose utilization and glycolysis are adapted to the different axonal energy demands. Spiking axons release glutamate and oligodendrocytes express NMDA receptors of unknown function. Here we show that the stimulation of oligodendroglial NMDA receptors mobilizes glucose transporter GLUT1, leading to its incorporation into the myelin compartment in vivo. When myelinated optic nerves from conditional NMDA receptor mutants are challenged with transient oxygen-glucose deprivation, they show a reduced functional recovery when returned to oxygen-glucose but are indistinguishable from wild-type when provided with oxygen-lactate. Moreover, the functional integrity of isolated optic nerves, which are electrically silent, is extended by preincubation with NMDA, mimicking axonal activity, and shortened by NMDA receptor blockers. This reveals a novel aspect of neuronal energy metabolismin which activity-dependent glutamate release enhances oligodendroglial glucose uptake and glycolytic support of fast spiking axons."],["dc.identifier.doi","10.1016/j.neuron.2016.05.016"],["dc.identifier.gro","3141651"],["dc.identifier.isi","000382394300016"],["dc.identifier.pmid","27292539"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5454"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1097-4199"],["dc.relation.issn","0896-6273"],["dc.title","Oligodendroglial NMDA Receptors Regulate Glucose Import and Axonal Energy Metabolism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","475"],["dc.bibliographiccitation.lastpage","512"],["dc.bibliographiccitation.seriesnr","96"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Cooper, Benjamin"],["dc.contributor.author","Kaufmann, Walter A."],["dc.contributor.author","Imig, Cordelia"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Saab, Aiman S."],["dc.contributor.author","Varoqueaux, Frédérique"],["dc.date.accessioned","2022-03-01T11:45:29Z"],["dc.date.available","2022-03-01T11:45:29Z"],["dc.date.issued","2010"],["dc.identifier.doi","10.1016/S0091-679X(10)96020-2"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103344"],["dc.notes.intern","DOI-Import GROB-531"],["dc.publisher","Elsevier"],["dc.relation.crisseries","Methods in Cell Biology"],["dc.relation.isbn","9780123810076"],["dc.relation.ispartof","Electron Microscopy of Model Systems"],["dc.title","Electron Microscopy of the Mouse Central Nervous System"],["dc.type","book_chapter"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","S2211124722002170"],["dc.bibliographiccitation.firstpage","110484"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Hösli, Ladina"],["dc.contributor.author","Binini, Noemi"],["dc.contributor.author","Ferrari, Kim David"],["dc.contributor.author","Thieren, Laetitia"],["dc.contributor.author","Looser, Zoe J."],["dc.contributor.author","Zuend, Marc"],["dc.contributor.author","Zanker, Henri S."],["dc.contributor.author","Berry, Stewart"],["dc.contributor.author","Holub, Martin"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Saab, Aiman S."],["dc.date.accessioned","2022-04-01T10:01:33Z"],["dc.date.available","2022-04-01T10:01:33Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1016/j.celrep.2022.110484"],["dc.identifier.pii","S2211124722002170"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105690"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.issn","2211-1247"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","Decoupling astrocytes in adult mice impairs synaptic plasticity and spatial learning"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["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"]]

[["dc.bibliographiccitation.artnumber","e24241"],["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Trevisiol, Andrea"],["dc.contributor.author","Saab, Aiman S."],["dc.contributor.author","Winkler, Ulrike"],["dc.contributor.author","Marx, Grit"],["dc.contributor.author","Imamura, Hiromi"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.date.accessioned","2017-05-22T13:48:50Z"],["dc.date.accessioned","2021-10-27T13:21:00Z"],["dc.date.available","2017-05-22T13:48:50Z"],["dc.date.available","2021-10-27T13:21:00Z"],["dc.date.issued","2017"],["dc.description.abstract","In several neurodegenerative diseases and myelin disorders, the degeneration profiles of myelinated axons are compatible with underlying energy deficits. However, it is presently impossible to measure selectively axonal ATP levels in the electrically active nervous system. We combined transgenic expression of an ATP-sensor in neurons of mice with confocal FRET imaging and electrophysiological recordings of acutely isolated optic nerves. This allowed us to monitor dynamic changes and activity-dependent axonal ATP homeostasis at the cellular level and in real time. We find that changes in ATP levels correlate well with compound action potentials. However, this correlation is disrupted when metabolism of lactate is inhibited, suggesting that axonal glycolysis products are not sufficient to maintain mitochondrial energy metabolism of electrically active axons. The combined monitoring of cellular ATP and electrical activity is a novel tool to study neuronal and glial energy metabolism in normal physiology and in models of neurodegenerative disorders."],["dc.identifier.doi","10.7554/eLife.24241"],["dc.identifier.pmid","28414271"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14464"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91987"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.issn","2050-084X"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Monitoring ATP dynamics in electrically active white matter tracts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4794"],["dc.bibliographiccitation.issue","15"],["dc.bibliographiccitation.journal","Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","4807"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Nawaz, Schanila"],["dc.contributor.author","Kippert, Angelika"],["dc.contributor.author","Saab, Aiman S."],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Lang, Thorsten"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T08:30:46Z"],["dc.date.available","2018-11-07T08:30:46Z"],["dc.date.issued","2009"],["dc.description.abstract","Myelin basic protein (MBP) is an essential structural component of CNS myelin. The electrostatic association of this positively charged protein with myelin-forming membranes is a crucial step in myelination, but the mechanism that regulates myelin membrane targeting is not known. Here, we demonstrate that phosphatidylinositol 4,5-bisphosphate (PIP2) is important for the stable association of MBP with cellular membranes. In oligodendrocytes, overexpression of synaptojanin 1-derived phosphoinositide 5-phosphatase, which selectively hydrolyzes membrane PIP2, causes the detachment of MBP from the plasma membrane. In addition, constitutively active Arf6/Q67L induces the formation of PIP2-enriched endosomal vacuoles, leading to the redistribution of MBP to intracellular vesicles. Fluorescence resonance energy transfer imaging revealed an interaction of the PIP2 sensing probe PH-PLC delta 1 with wild-type MBP, but not with a mutant MBP isoform that fails to associate with the plasma membrane. Moreover, increasing intracellular Ca(2+), followed by phospholipase C-mediated PIP2 hydrolysis, as well as reduction of the membrane charge by ATP depletion, resulted in the dissociation of MBP from the glial plasma membrane. When the corpus callosum of mice was analyzed in acute brain slices by electron microscopy, the reduction of membrane surface charge led to the loss of myelin compaction and rapid vesiculation. Together, these results establish that PIP2 is an essential determinant for stable membrane binding of MBP and provide a novel link between glial phosphoinositol metabolism and MBP function in development and disease."],["dc.identifier.doi","10.1523/JNEUROSCI.3955-08.2009"],["dc.identifier.isi","000265232000011"],["dc.identifier.pmid","19369548"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16971"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Soc Neuroscience"],["dc.relation.issn","0270-6474"],["dc.title","Phosphatidylinositol 4,5-Bisphosphate-Dependent Interaction of Myelin Basic Protein with the Plasma Membrane in Oligodendroglial Cells and Its Rapid Perturbation by Elevated Calcium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]