Möbius, Wiebke

[["dc.bibliographiccitation.artnumber","e1006290"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","PLoS genetics"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Hu, Bo"],["dc.contributor.author","Arpag, Sezgi"],["dc.contributor.author","Zhang, Xuebao"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Werner, Hauke"],["dc.contributor.author","Sosinsky, Gina"],["dc.contributor.author","Ellisman, Mark"],["dc.contributor.author","Zhang, Yang"],["dc.contributor.author","Hamilton, Audra"],["dc.contributor.author","Chernoff, Jonathan"],["dc.contributor.author","Li, Jun"],["dc.date.accessioned","2019-07-09T11:42:46Z"],["dc.date.available","2019-07-09T11:42:46Z"],["dc.date.issued","2016-09-01"],["dc.description.abstract","Schwann cells in the peripheral nervous systems extend their membranes to wrap axons concentrically and form the insulating sheath, called myelin. The spaces between layers of myelin are sealed by myelin junctions. This tight insulation enables rapid conduction of electric impulses (action potentials) through axons. Demyelination (stripping off the insulating sheath) has been widely regarded as one of the most important mechanisms altering the action potential propagation in many neurological diseases. However, the effective nerve conduction is also thought to require a proper myelin seal through myelin junctions such as tight junctions and adherens junctions. In the present study, we have demonstrated the disruption of myelin junctions in a mouse model (Pmp22+/-) of hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of Pmp22 gene. We observed a robust increase of F-actin in Pmp22+/- nerve regions where myelin junctions were disrupted, leading to increased myelin permeability. These abnormalities were present long before segmental demyelination at the late phase of Pmp22+/- mice. Moreover, the increase of F-actin levels correlated with an enhanced activity of p21-activated kinase (PAK1), a molecule known to regulate actin polymerization. Pharmacological inhibition of PAK normalized levels of F-actin, and completely prevented the progression of the myelin junction disruption and nerve conduction failure in Pmp22+/- mice. Our findings explain how abnormal myelin permeability is caused in HNPP, leading to impaired action potential propagation in the absence of demyelination. We call it \"functional demyelination\", a novel mechanism upstream to the actual stripping of myelin that is relevant to many demyelinating diseases. This observation also provides a potential therapeutic approach for HNPP."],["dc.identifier.doi","10.1371/journal.pgen.1006290"],["dc.identifier.pmid","27583434"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13698"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58738"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1553-7404"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Tuning PAK Activity to Rescue Abnormal Myelin Permeability in HNPP."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e3000943"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Trevisiol, Andrea"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Steyer, Anna M."],["dc.contributor.author","Gregor, Ingo"],["dc.contributor.author","Nardis, Christos"],["dc.contributor.author","Winkler, Ulrike"],["dc.contributor.author","Köhler, Susanne"],["dc.contributor.author","Restrepo, Alejandro"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.date.accessioned","2021-04-14T08:31:16Z"],["dc.date.available","2021-04-14T08:31:16Z"],["dc.date.issued","2020"],["dc.description.abstract","In several neurodegenerative disorders, axonal pathology may originate from impaired oligodendrocyte-to-axon support of energy substrates. We previously established transgenic mice that allow measuring axonal ATP levels in electrically active optic nerves. Here, we utilize this technique to explore axonal ATP dynamics in the Plpnull/y mouse model of spastic paraplegia. Optic nerves from Plpnull/y mice exhibited lower and more variable basal axonal ATP levels and reduced compound action potential (CAP) amplitudes, providing a missing link between axonal pathology and a role of oligodendrocytes in brain energy metabolism. Surprisingly, when Plpnull/y optic nerves are challenged with transient glucose deprivation, both ATP levels and CAP decline slower, but recover faster upon reperfusion of glucose. Structurally, myelin sheaths display an increased frequency of cytosolic channels comprising glucose and monocarboxylate transporters, possibly facilitating accessibility of energy substrates to the axon. These data imply that complex metabolic alterations of the axon–myelin unit contribute to the phenotype of Plpnull/y mice."],["dc.identifier.doi","10.1371/journal.pbio.3000943"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83539"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/20"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala"],["dc.relation","FOR 2848 | P08: Strukturelle und funktionale Veränderungen der inneren mitochondrialen Membran axonaler Mitochondrien in vivo in einem dymyelinisierenden Mausmodell"],["dc.relation.eissn","1545-7885"],["dc.relation.workinggroup","RG Möbius"],["dc.rights","CC BY 4.0"],["dc.title","Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6367"],["dc.bibliographiccitation.issue","22"],["dc.bibliographiccitation.journal","Theranostics"],["dc.bibliographiccitation.lastpage","6383"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Napp, Joanna"],["dc.contributor.author","Markus, M. Andrea"],["dc.contributor.author","Heck, Joachim G."],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Gorpas, Dimitris"],["dc.contributor.author","Feldmann, Claus"],["dc.contributor.author","Alves, Frauke"],["dc.date.accessioned","2019-07-09T11:49:44Z"],["dc.date.available","2019-07-09T11:49:44Z"],["dc.date.issued","2018"],["dc.description.abstract","Treatment of inflammatory disorders with glucocorticoids (GCs) is often accompanied by severe adverse effects. Application of GCs via nanoparticles (NPs), especially those using simple formulations, could possibly improve their delivery to sites of inflammation and therefore their efficacy, minimising the required dose and thus reducing side effects. Here, we present the evaluation of NPs composed of GC betamethasone phosphate (BMP) and the fluorescent dye DY-647 (BMP-IOH-NPs) for improved treatment of inflammation with simultaneous in vivo monitoring of NP delivery. Methods: BMP-IOH-NP uptake by MH-S macrophages was analysed by fluorescence and electron microscopy. Lipopolysaccharide (LPS)-stimulated cells were treated for 48 h with BMP-IOH-NPs (1×10-5-1×10-9 M), BMP or dexamethasone (Dexa). Drug efficacy was assessed by measurement of interleukin 6. Mice with Zymosan-A-induced paw inflammation were intraperitoneally treated with BMP-IOH-NPs (10 mg/kg) and mice with ovalbumin (OVA)-induced allergic airway inflammation (AAI) were treated intranasally with BMP-IOH-NPs, BMP or Dexa (each 2.5 mg/kg). Efficacy was assessed in vivo by paw volume measurements with µCT and ex vivo by measurement of paw weight for Zymosan-A-treated mice, or in the AAI model by in vivo x-ray-based lung function assessment and by cell counts in the bronchoalveolar lavage (BAL) fluid and histology. Delivery of BMP-IOH-NPs to the lungs of AAI mice was monitored by in vivo optical imaging and by fluorescence microscopy. Results: Uptake of BMP-IOH-NPs by MH-S cells was observed during the first 10 min of incubation, with the NP load increasing over time. The anti-inflammatory effect of BMP-IOH-NPs in vitro was dose dependent and higher than that of Dexa or free BMP, confirming efficient release of the drug. In vivo, Zymosan-A-induced paw inflammation was significantly reduced in mice treated with BMP-IOH-NPs. AAI mice that received BMP-IOH-NPs or Dexa but not BMP revealed significantly decreased eosinophil numbers in BALs and reduced immune cell infiltration in lungs. Correspondingly, lung function parameters, which were strongly affected in non-treated AAI mice, were unaffected in AAI mice treated with BMP-IOH-NPs and resembled those of healthy animals. Accumulation of BMP-IOH-NPs within the lungs of AAI mice was detectable by optical imaging for at least 4 h in vivo, where they were preferentially taken up by peribronchial and alveolar M2 macrophages. Conclusion: Our results show that BMP-IOH-NPs can effectively be applied in therapy of inflammatory diseases with at least equal efficacy as the gold standard Dexa, while their delivery can be simultaneously tracked in vivo by fluorescence imaging. BMP-IOH-NPs thus have the potential to reach clinical applications."],["dc.identifier.doi","10.7150/thno.28324"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15757"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59620"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1838-7640"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.subject.ddc","610"],["dc.title","Therapeutic Fluorescent Hybrid Nanoparticles for Traceable Delivery of Glucocorticoids to Inflammatory Sites"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","673"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","674"],["dc.bibliographiccitation.volume","138"],["dc.contributor.author","Stumpf, Sina K."],["dc.contributor.author","Berghoff, Stefan A."],["dc.contributor.author","Trevisiol, Andrea"],["dc.contributor.author","Spieth, Lena"],["dc.contributor.author","Düking, Tim"],["dc.contributor.author","Schneider, Lennart V."],["dc.contributor.author","Schlaphoff, Lennart"],["dc.contributor.author","Dreha-Kulaczewski, Steffi"],["dc.contributor.author","Bley, Annette"],["dc.contributor.author","Burfeind, Dinah"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Mitkovski, Miso"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Guder, Philipp"],["dc.contributor.author","Röhse, Heiko"],["dc.contributor.author","Denecke, Jonas"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Saher, Gesine"],["dc.date.accessioned","2019-11-04T14:10:22Z"],["dc.date.accessioned","2021-10-27T13:21:24Z"],["dc.date.available","2019-11-04T14:10:22Z"],["dc.date.available","2021-10-27T13:21:24Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1007/s00401-019-02064-2"],["dc.identifier.pmid","31482207"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16592"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92019"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1432-0533"],["dc.relation.iserratumof","/handle/2/62293"],["dc.relation.issn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Correction to: Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus–Merzbacher disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","erratum_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1840"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Fledrich, Robert"],["dc.contributor.author","Akkermann, Dagmar"],["dc.contributor.author","Schütza, Vlad"],["dc.contributor.author","Abdelaal, Tamer A."],["dc.contributor.author","Hermes, Doris"],["dc.contributor.author","Schäffner, Erik"],["dc.contributor.author","Soto-Bernardini, M. Clara"],["dc.contributor.author","Götze, Tilmann"],["dc.contributor.author","Klink, Axel"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Krueger, Martin"],["dc.contributor.author","Kungl, Theresa"],["dc.contributor.author","Frydrychowicz, Clara"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Mueller, Wolf C."],["dc.contributor.author","Bechmann, Ingo"],["dc.contributor.author","Sereda, Michael W."],["dc.contributor.author","Schwab, Markus H."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Stassart, Ruth M."],["dc.date.accessioned","2019-07-09T11:51:38Z"],["dc.date.available","2019-07-09T11:51:38Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1038/s41467-019-09886-4"],["dc.identifier.pmid","30992451"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16160"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59979"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Publisher Correction: NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","012001"],["dc.bibliographiccitation.journal","Journal of Physics. Conference Series"],["dc.bibliographiccitation.volume","849"],["dc.contributor.author","Töpperwien, Mareike"],["dc.contributor.author","Krenkel, Martin"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Pacureanu, A."],["dc.contributor.author","Cloetens, Peter"],["dc.contributor.author","Salditt, Tim"],["dc.date.accessioned","2020-03-11T09:13:55Z"],["dc.date.available","2020-03-11T09:13:55Z"],["dc.date.issued","2017"],["dc.description.abstract","We present propagation-based phase-contrast tomography of mouse sciatic nerves stained with osmium, leading to an enhanced contrast in the myelin sheath around the axons, in order to visualize the threedimensional (3D) structure of the nerve. We compare different experimental parameters and show that contrast and resolution are high enough to identify single axons in the nerve, including characteristic functional structures such as Schmidt-Lanterman incisures."],["dc.identifier.doi","10.1088/1742-6596/849/1/012001"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63293"],["dc.language.iso","en"],["dc.relation.issn","1742-6588"],["dc.relation.issn","1742-6596"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics)"],["dc.rights","CC BY 3.0"],["dc.subject.gro","x-ray imaging"],["dc.subject.gro","biomedical tomography"],["dc.title","Phase-contrast tomography of sciatic nerves: image quality and experimental parameters"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1467"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Fledrich, Robert"],["dc.contributor.author","Akkermann, Dagmar"],["dc.contributor.author","Schütza, Vlad"],["dc.contributor.author","Abdelaal, Tamer A."],["dc.contributor.author","Hermes, Doris"],["dc.contributor.author","Schäffner, Erik"],["dc.contributor.author","Soto-Bernardini, M. Clara"],["dc.contributor.author","Götze, Tilmann"],["dc.contributor.author","Klink, Axel"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Krueger, Martin"],["dc.contributor.author","Kungl, Theresa"],["dc.contributor.author","Frydrychowicz, Clara"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Mueller, Wolf C."],["dc.contributor.author","Bechmann, Ingo"],["dc.contributor.author","Sereda, Michael W."],["dc.contributor.author","Schwab, Markus H."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Stassart, Ruth M."],["dc.date.accessioned","2019-07-09T11:50:53Z"],["dc.date.available","2019-07-09T11:50:53Z"],["dc.date.issued","2019"],["dc.description.abstract","In contrast to acute peripheral nerve injury, the molecular response of Schwann cells in chronic neuropathies remains poorly understood. Onion bulb structures are a pathological hallmark of demyelinating neuropathies, but the nature of these formations is unknown. Here, we show that Schwann cells induce the expression of Neuregulin-1 type I (NRG1-I), a paracrine growth factor, in various chronic demyelinating diseases. Genetic disruption of Schwann cell-derived NRG1 signalling in a mouse model of Charcot-Marie-Tooth Disease 1A (CMT1A), suppresses hypermyelination and the formation of onion bulbs. Transgenic overexpression of NRG1-I in Schwann cells on a wildtype background is sufficient to mediate an interaction between Schwann cells via an ErbB2 receptor-MEK/ERK signaling axis, which causes onion bulb formations and results in a peripheral neuropathy reminiscent of CMT1A. We suggest that diseased Schwann cells mount a regeneration program that is beneficial in acute nerve injury, but that overstimulation of Schwann cells in chronic neuropathies is detrimental."],["dc.identifier.doi","10.1038/s41467-019-09385-6"],["dc.identifier.pmid","30931926"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16018"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59847"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2693"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.lastpage","2699"],["dc.bibliographiccitation.volume","107"],["dc.contributor.author","Nolting, Jens-Friedrich"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Köster, Sarah"],["dc.date.accessioned","2017-09-07T11:45:22Z"],["dc.date.available","2017-09-07T11:45:22Z"],["dc.date.issued","2014"],["dc.description.abstract","Along with microtubules and microfilaments, intermediate filaments are a major component of the eukaryotic cytoskeleton and play a key role in cell mechanics. In cells, keratin intermediate filaments form networks of bundles that are sparser in structure and have lower connectivity than, for example, actin networks. Because of this, bending and buckling play an important role in these networks. Buckling events, which occur due to compressive intracellular forces and cross-talk between the keratin network and other cytoskeletal components, are measured here in situ. By applying a mechanical model for the bundled filaments, we can access the mechanical properties of both the keratin bundles themselves and the surrounding cytosol. Bundling is characterized by a coupling parameter that describes the strength of the linkage between the individual filaments within a bundle. Our findings suggest that coupling between the filaments is mostly complete, although it becomes weaker for thicker bundles, with some relative movement allowed."],["dc.identifier.doi","10.1016/j.bpj.2014.10.039"],["dc.identifier.gro","3142001"],["dc.identifier.isi","000345859500029"],["dc.identifier.pmid","25468348"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3445"],["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","1542-0086"],["dc.relation.issn","0006-3495"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Köster (Cellular Biophysics)"],["dc.rights","CC BY-NC-ND 3.0"],["dc.subject.gro","cytoskeleton"],["dc.subject.gro","cellular biophysics"],["dc.title","Mechanics of Individual Keratin Bundles in Living Cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","S1047847720300587"],["dc.bibliographiccitation.firstpage","107492"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Structural Biology"],["dc.bibliographiccitation.volume","210"],["dc.contributor.author","Steyer, Anna M."],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Nardis, Christos"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Möbius, Wiebke"],["dc.date.accessioned","2022-03-01T11:45:16Z"],["dc.date.available","2022-03-01T11:45:16Z"],["dc.date.issued","2020"],["dc.description.abstract","Advances in electron microscopy including improved imaging techniques and state-of-the-art detectors facilitate imaging of larger tissue volumes with electron microscopic resolution. In combination with genetic tools for the generation of mouse mutants this allows assessing the three-dimensional (3D) characteristics of pathological features in disease models. Here we revisited the axonal pathology in the central nervous system of a mouse model of spastic paraplegia type 2, the Plp−/Y mouse. Although PLP is a bona fide myelin protein, the major hallmark of the disease in both SPG2 patients and mouse models are axonal swellings comprising accumulations of numerous organelles including mitochondria, gradually leading to irreversible axonal loss. To assess the number and morphology of axonal mitochondria and the overall myelin preservation we evaluated two sample preparation techniques, chemical fixation or high-pressure freezing and freeze substitution, with respect to the objective of 3D visualization. Both methods allowed visualizing distribution and morphological details of axonal mitochondria. In Plp−/Y mice the number of mitochondria is 2-fold increased along the entire axonal length. Mitochondria are also found in the excessive organelle accumulations within axonal swellings. In addition, organelle accumulations were detected within the myelin sheath and the inner tongue. We find that 3D electron microscopy is required for a comprehensive understanding of the size, content and frequency of axonal swellings, the hallmarks of axonal pathology."],["dc.identifier.doi","10.1016/j.jsb.2020.107492"],["dc.identifier.pii","S1047847720300587"],["dc.identifier.pmid","32156581"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103268"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/23"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation","FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala"],["dc.relation","FOR 2848 | P08: Strukturelle und funktionale Veränderungen der inneren mitochondrialen Membran axonaler Mitochondrien in vivo in einem dymyelinisierenden Mausmodell"],["dc.relation.issn","1047-8477"],["dc.relation.workinggroup","RG Möbius"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","Pathology of myelinated axons in the PLP-deficient mouse model of spastic paraplegia type 2 revealed by volume imaging using focused ion beam-scanning electron microscopy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","281"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","298"],["dc.bibliographiccitation.volume","131"],["dc.contributor.author","Syed, Yasir A."],["dc.contributor.author","Zhao, Chao"],["dc.contributor.author","Mahad, Don"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Altmann, Friedrich"],["dc.contributor.author","Foss, Franziska"],["dc.contributor.author","Sentuerk, Aycan"],["dc.contributor.author","Acker-Palmer, Amparo"],["dc.contributor.author","Lubec, Gert"],["dc.contributor.author","Lilley, Kathryn"],["dc.contributor.author","Franklin, Robin J. M."],["dc.contributor.author","Nave, Klaus-A."],["dc.contributor.author","Kotter, Mark R. N."],["dc.date.accessioned","2018-11-07T10:18:56Z"],["dc.date.available","2018-11-07T10:18:56Z"],["dc.date.issued","2016"],["dc.description.abstract","Remyelination in multiple sclerosis (MS) lesions often remains incomplete despite the presence of oligodendrocyte progenitor cells (OPCs). Amongst other factors, successful remyelination depends on the phagocytic clearance of myelin debris. However, the proteins in myelin debris that act as potent and selective inhibitors on OPC differentiation and inhibit CNS remyelination remain unknown. Here, we identify the transmembrane signalling protein EphrinB3 as important mediator of this inhibition, using a protein analytical approach in combination with a primary rodent OPC assay. In the presence of EphrinB3, OPCs fail to differentiate. In a rat model of remyelination, infusion of EphrinB3 inhibits remyelination. In contrast, masking EphrinB3 epitopes using antibodies promotes remyelination. Finally, we identify EphrinB3 in MS lesions and demonstrate that MS lesion extracts inhibit OPC differentiation while antibody-mediated masking of EphrinB3 epitopes promotes it. Our findings suggest that EphrinB3 could be a target for therapies aiming at promoting remyelination in demyelinating disease."],["dc.description.sponsorship","UK MS Society [941/11]; ERC advanced award"],["dc.identifier.doi","10.1007/s00401-015-1521-1"],["dc.identifier.isi","000368535000008"],["dc.identifier.pmid","26687980"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12896"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41553"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Antibody-mediated neutralization of myelin-associated EphrinB3 accelerates CNS remyelination"],["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"]]