Schifferer, Martina

[["dc.bibliographiccitation.artnumber","e2200302"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","Small"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Khalin, Igor"],["dc.contributor.author","Adarsh, Nagappanpillai"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Wehn, Antonia"],["dc.contributor.author","Groschup, Bernhard"],["dc.contributor.author","Misgeld, Thomas"],["dc.contributor.author","Klymchenko, Andrey"],["dc.contributor.author","Plesnila, Nikolaus"],["dc.date.accessioned","2022-08-19T08:02:00Z"],["dc.date.available","2022-08-19T08:02:00Z"],["dc.date.issued","2022"],["dc.description.abstract","The current lack of understanding about how nanocarriers cross the blood-brain barrier (BBB) in the healthy and injured brain is hindering the clinical translation of nanoscale brain-targeted drug-delivery systems. Here, the bio-distribution of lipid nano-emulsion droplets (LNDs) of two sizes (30 and 80 nm) in the mouse brain after traumatic brain injury (TBI) is investigated. The highly fluorescent LNDs are prepared by loading them with octadecyl rhodamine B and a bulky hydrophobic counter-ion, tetraphenylborate. Using in vivo two-photon and confocal imaging, the circulation kinetics and bio-distribution of LNDs in the healthy and injured mouse brain are studied. It is found that after TBI, LNDs of both sizes accumulate at vascular occlusions, where specifically 30 nm LNDs extravasate into the brain parenchyma and reach neurons. The vascular occlusions are not associated with bleedings, but instead are surrounded by processes of activated microglia, suggesting a specific opening of the BBB. Finally, correlative light-electron microscopy reveals 30 nm LNDs in endothelial vesicles, while 80 nm particles remain in the vessel lumen, indicating size-selective vesicular transport across the BBB via vascular occlusions. The data suggest that microvascular occlusions serve as \"gates\" for the transport of nanocarriers across the BBB."],["dc.identifier.doi","10.1002/smll.202200302"],["dc.identifier.pmid","35384294"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113025"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/63"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | Z01: Bioimaging Platform"],["dc.relation.eissn","1613-6829"],["dc.relation.issn","1613-6810"],["dc.relation.workinggroup","RG Misgeld"],["dc.relation.workinggroup","RG Schifferer"],["dc.title","Size-Selective Transfer of Lipid Nanoparticle-Based Drug Carriers Across the Blood Brain Barrier Via Vascular Occlusions Following Traumatic Brain Injury"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.contributor.author","Djannatian, Minou"],["dc.contributor.author","Weikert, Ulrich"],["dc.contributor.author","Safaiyan, Shima"],["dc.contributor.author","Wrede, Christoph"],["dc.contributor.author","Deichsel, Cassandra"],["dc.contributor.author","Kislinger, Georg"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Campbell, Douglas S."],["dc.contributor.author","van Ham, Tjakko"],["dc.contributor.author","Schmid, Bettina"],["dc.contributor.author","Hegermann, Jan"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2022-08-19T08:17:44Z"],["dc.date.available","2022-08-19T08:17:44Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1101/2021.02.02.429485"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113031"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/14"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis"],["dc.relation.workinggroup","RG Schifferer"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","Myelin biogenesis is associated with pathological ultrastructure that is resolved by microglia during development"],["dc.type","preprint"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Journal of Experimental Medicine"],["dc.bibliographiccitation.volume","218"],["dc.contributor.author","Gouna, Garyfallia"],["dc.contributor.author","Klose, Christian"],["dc.contributor.author","Bosch-Queralt, Mar"],["dc.contributor.author","Liu, Lu"],["dc.contributor.author","Gokce, Ozgun"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Cantuti-Castelvetri, Ludovico"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2022-08-19T07:04:48Z"],["dc.date.available","2022-08-19T07:04:48Z"],["dc.date.issued","2021"],["dc.description.abstract","Upon demyelinating injury, microglia orchestrate a regenerative response that promotes myelin repair, thereby restoring rapid signal propagation and protecting axons from further damage. Whereas the essential phagocytic function of microglia for remyelination is well known, the underlying metabolic pathways required for myelin debris clearance are poorly understood. Here, we show that cholesterol esterification in male mouse microglia/macrophages is a necessary adaptive response to myelin debris uptake and required for the generation of lipid droplets upon demyelinating injury. When lipid droplet biogenesis is defective, innate immune cells do not resolve, and the regenerative response fails. We found that triggering receptor expressed on myeloid cells 2 (TREM2)-deficient mice are unable to adapt to excess cholesterol exposure, form fewer lipid droplets, and build up endoplasmic reticulum (ER) stress. Alleviating ER stress in TREM2-deficient mice restores lipid droplet biogenesis and resolves the innate immune response. Thus, we conclude that TREM2-dependent formation of lipid droplets constitute a protective response required for remyelination to occur."],["dc.identifier.doi","10.1084/jem.20210227"],["dc.identifier.pmid","34424266"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113016"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/41"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis"],["dc.relation.eissn","1540-9538"],["dc.relation.issn","0022-1007"],["dc.relation.workinggroup","RG Cantuti"],["dc.relation.workinggroup","RG Gokce (Systems Neuroscience – Cell Diversity)"],["dc.relation.workinggroup","RG Schifferer"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","259.e10"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell Metabolism"],["dc.bibliographiccitation.lastpage","272.e10"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Mukherjee, Chaitali"],["dc.contributor.author","Kling, Tina"],["dc.contributor.author","Russo, Belisa"],["dc.contributor.author","Miebach, Kerstin"],["dc.contributor.author","Kess, Eva"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Pedro, Liliana D."],["dc.contributor.author","Weikert, Ulrich"],["dc.contributor.author","Fard, Maryam K."],["dc.contributor.author","Kannaiyan, Nirmal"],["dc.contributor.author","Rossner, Moritz"],["dc.contributor.author","Aicher, Marie-Louise"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Krämer-Albers, Eva-Maria"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2022-08-18T13:15:19Z"],["dc.date.available","2022-08-18T13:15:19Z"],["dc.date.issued","2020"],["dc.description.abstract","An evolutionarily conserved function of glia is to provide metabolic and structural support for neurons. To identify molecules generated by glia and with vital functions for neurons, we used Drosophila melanogaster as a screening tool, and subsequently translated the findings to mice. We found that a cargo receptor operating in the secretory pathway of glia was essential to maintain axonal integrity by regulating iron buffering. Ferritin heavy chain was identified as the critical secretory cargo, required for the protection against iron-mediated ferroptotic axonal damage. In mice, ferritin heavy chain is highly expressed by oligodendrocytes and secreted by employing an unconventional secretion pathway involving extracellular vesicles. Disrupting the release of extracellular vesicles or the expression of ferritin heavy chain in oligodendrocytes causes neuronal loss and oxidative damage in mice. Our data point to a role of oligodendrocytes in providing an antioxidant defense system to support neurons against iron-mediated cytotoxicity."],["dc.identifier.doi","10.1016/j.cmet.2020.05.019"],["dc.identifier.pmid","32531201"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113000"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/4"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis"],["dc.relation.eissn","1932-7420"],["dc.relation.issn","1550-4131"],["dc.relation.workinggroup","RG Nave (Neurogenetics)"],["dc.relation.workinggroup","RG Schifferer"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Journal of Experimental Medicine"],["dc.bibliographiccitation.volume","217"],["dc.contributor.author","Cunha, Maria Inês"],["dc.contributor.author","Su, Minhui"],["dc.contributor.author","Cantuti-Castelvetri, Ludovico"],["dc.contributor.author","Müller, Stephan A."],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Djannatian, Minou"],["dc.contributor.author","Alexopoulos, Ioannis"],["dc.contributor.author","van der Meer, Franziska"],["dc.contributor.author","Winkler, Anne"],["dc.contributor.author","van Ham, Tjakko J."],["dc.contributor.author","Schmid, Bettina"],["dc.contributor.author","Lichtenthaler, Stefan F."],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2020-12-10T18:15:37Z"],["dc.date.available","2020-12-10T18:15:37Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1084/jem.20191390"],["dc.identifier.pmid","32078678"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/74902"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/24"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis"],["dc.relation.workinggroup","RG Cantuti"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.relation.workinggroup","RG Schifferer"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.title","Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4901"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Mezydlo, Aleksandra"],["dc.contributor.author","Zalc, Bernard"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.contributor.author","Misgeld, Thomas"],["dc.date.accessioned","2022-08-18T13:29:08Z"],["dc.date.available","2022-08-18T13:29:08Z"],["dc.date.issued","2020"],["dc.description.abstract","Myelin, rather than being a static insulator of axons, is emerging as an active participant in circuit plasticity. This requires precise regulation of oligodendrocyte numbers and myelination patterns. Here, by devising a laser ablation approach of single oligodendrocytes, followed by in vivo imaging and correlated ultrastructural reconstructions, we report that in mouse cortex demyelination as subtle as the loss of a single oligodendrocyte can trigger robust cell replacement and remyelination timed by myelin breakdown. This results in reliable reestablishment of the original myelin pattern along continuously myelinated axons, while in parallel, patchy isolated internodes emerge on previously unmyelinated axons. Therefore, in mammalian cortex, internodes along partially myelinated cortical axons are typically not reestablished, suggesting that the cues that guide patchy myelination are not preserved through cycles of de- and remyelination. In contrast, myelin sheaths forming continuous patterns show remarkable homeostatic resilience and remyelinate with single axon precision."],["dc.identifier.doi","10.1038/s41467-020-18632-0"],["dc.identifier.pmid","32994410"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113004"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/7"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B02: Inflammatory neurodegeneration and repair mechanisms in childhood onset autoimmune and neurometabolic demyelinating CNS disease"],["dc.relation","TRR 274 | C02: In vivo detection and targeting of calcium clearance and axonal membrane repair after acute CNS insults"],["dc.relation","TRR 274 | C05: Checkpoints for circuit integration of nascent neurons in the injured brain"],["dc.relation","TRR 274 | Z01: Bioimaging Platform"],["dc.relation.issn","2041-1723"],["dc.relation.workinggroup","RG Kerschensteiner (Neuroimmune Interactions)"],["dc.relation.workinggroup","RG Misgeld"],["dc.relation.workinggroup","RG Schifferer"],["dc.title","Myelin replacement triggered by single-cell demyelination in mouse cortex"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","100232"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","STAR Protocols"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Kislinger, Georg"],["dc.contributor.author","Gnägi, Helmut"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Misgeld, Thomas"],["dc.contributor.author","Schifferer, Martina"],["dc.date.accessioned","2022-08-19T06:32:51Z"],["dc.date.available","2022-08-19T06:32:51Z"],["dc.date.issued","2020"],["dc.description.abstract","Here, we describe a detailed workflow for ATUM-FIB microscopy, a hybrid method that combines serial-sectioning scanning electron microscopy (SEM) with focused ion beam SEM (FIB-SEM). This detailed protocol is optimized for mouse cortex samples. The main processing steps include the generation of semi-thick sections from sequentially cured resin blocks using a heated microtomy approach. We demonstrate the different imaging modalities, including serial light and electron microscopy for target recognition and FIB-SEM for isotropic imaging of regions of interest. For complete details on the use and execution of this protocol, please refer to Kislinger et al. (2020)."],["dc.identifier.doi","10.1016/j.xpro.2020.100232"],["dc.identifier.pmid","33377119"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113013"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/33"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B03: Checkpoints of recovery after primary astrocytic lesions in neuromyelitis optica and related animal models"],["dc.relation","TRR 274 | C02: In vivo detection and targeting of calcium clearance and axonal membrane repair after acute CNS insults"],["dc.relation","TRR 274 | Z01: Bioimaging Platform"],["dc.relation.eissn","2666-1667"],["dc.relation.workinggroup","RG Kerschensteiner (Neuroimmune Interactions)"],["dc.relation.workinggroup","RG Misgeld"],["dc.relation.workinggroup","RG Schifferer"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","ATUM-FIB microscopy for targeting and multiscale imaging of rare events in mouse cortex"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","101290"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","iScience"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Kislinger, Georg"],["dc.contributor.author","Gnägi, Helmut"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Misgeld, Thomas"],["dc.contributor.author","Schifferer, Martina"],["dc.date.accessioned","2022-08-18T13:58:23Z"],["dc.date.available","2022-08-18T13:58:23Z"],["dc.date.issued","2020-07-24"],["dc.description.abstract","Volume electron microscopy enables the ultrastructural analysis of biological tissue. Currently, the techniques involving ultramicrotomy (ATUM, ssTEM) allow large fields of view but afford only limited z-resolution, whereas ion beam-milling approaches (FIB-SEM) yield isotropic voxels but are restricted in volume size. Now we present a hybrid method, named ATUM-FIB, which combines the advantages of both approaches. ATUM-FIB is based on serial sectioning of tissue into \"semithick\" (2-10 μm) sections collected onto tape. Serial light and electron microscopy allows the identification of regions of interest that are then directly accessible for targeted FIB-SEM. The set of semithick sections thus represents a tissue \"library\" which provides three-dimensional context information that can be probed \"on demand\" by local high-resolution analysis. We demonstrate the potential of this technique to reveal the ultrastructure of rare but pathologically important events by identifying microglia contact sites with amyloid plaques in a mouse model of familial Alzheimer's disease."],["dc.identifier.doi","10.1016/j.isci.2020.101290"],["dc.identifier.pmid","32622266"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113006"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/15"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B03: Checkpoints of recovery after primary astrocytic lesions in neuromyelitis optica and related animal models"],["dc.relation","TRR 274 | C02: In vivo detection and targeting of calcium clearance and axonal membrane repair after acute CNS insults"],["dc.relation","TRR 274 | Z01: Bioimaging Platform"],["dc.relation.eissn","2589-0042"],["dc.relation.workinggroup","RG Kerschensteiner (Neuroimmune Interactions)"],["dc.relation.workinggroup","RG Misgeld"],["dc.relation.workinggroup","RG Schifferer"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","Multiscale ATUM-FIB Microscopy Enables Targeted Ultrastructural Analysis at Isotropic Resolution"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","211"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Nature Metabolism"],["dc.bibliographiccitation.lastpage","227"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Bosch-Queralt, Mar"],["dc.contributor.author","Cantuti-Castelvetri, Ludovico"],["dc.contributor.author","Damkou, Alkmini"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Schlepckow, Kai"],["dc.contributor.author","Alexopoulos, Ioannis"],["dc.contributor.author","Lütjohann, Dieter"],["dc.contributor.author","Klose, Christian"],["dc.contributor.author","Vaculčiaková, Lenka"],["dc.contributor.author","Masuda, Takahiro"],["dc.contributor.author","Prinz, Marco"],["dc.contributor.author","Monroe, Kathryn M."],["dc.contributor.author","Di Paolo, Gilbert"],["dc.contributor.author","Lewcock, Joseph W."],["dc.contributor.author","Haass, Christian"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2022-08-18T14:19:20Z"],["dc.date.available","2022-08-18T14:19:20Z"],["dc.date.issued","2021"],["dc.description.abstract","Proregenerative responses are required for the restoration of nervous-system functionality in demyelinating diseases such as multiple sclerosis (MS). Yet, the limiting factors responsible for poor CNS repair are only partially understood. Here, we test the impact of a Western diet (WD) on phagocyte function in a mouse model of demyelinating injury that requires microglial innate immune function for a regenerative response to occur. We find that WD feeding triggers an ageing-related, dysfunctional metabolic response that is associated with impaired myelin-debris clearance in microglia, thereby impairing lesion recovery after demyelination. Mechanistically, we detect enhanced transforming growth factor beta (TGFβ) signalling, which suppresses the activation of the liver X receptor (LXR)-regulated genes involved in cholesterol efflux, thereby inhibiting phagocytic clearance of myelin and cholesterol. Blocking TGFβ or promoting triggering receptor expressed on myeloid cells 2 (TREM2) activity restores microglia responsiveness and myelin-debris clearance after demyelinating injury. Thus, we have identified a druggable microglial immune checkpoint mechanism regulating the microglial response to injury that promotes remyelination."],["dc.identifier.doi","10.1038/s42255-021-00341-7"],["dc.identifier.pmid","33619376"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113011"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/25"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis"],["dc.relation.issn","2522-5812"],["dc.relation.workinggroup","RG Cantuti"],["dc.relation.workinggroup","RG Schifferer"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","Diet-dependent regulation of TGFβ impairs reparative innate immune responses after demyelination"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Brain"],["dc.contributor.author","Herwerth, Marina"],["dc.contributor.author","Kenet, Selin"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Winkler, Anne"],["dc.contributor.author","Weber, Melanie"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Wang, Mengzhe"],["dc.contributor.author","Lohrberg, Melanie"],["dc.contributor.author","Bennett, Jeffrey L."],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Misgeld, Thomas"],["dc.date.accessioned","2022-04-01T10:02:49Z"],["dc.date.available","2022-04-01T10:02:49Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract Neuromyelitis optica (NMO) is a chronic neuroinflammatory disease, which primarily targets astrocytes and often results in severe axon injury of unknown mechanism. NMO patients harbor autoantibodies against the astrocytic water channel protein, aquaporin-4 (AQP4-IgG), which induce complement-mediated astrocyte lysis and subsequent axon damage. Using spinal in vivo imaging in a mouse model of such astrocytopathic lesions, we explored the mechanism underlying NMO-related axon injury. Many axons showed a swift and morphologically distinct ‘pearls-on-string’ transformation also readily detectable in human NMO lesions, which especially affected small caliber axons independently of myelination. Functional imaging revealed that calcium homeostasis was initially preserved in this ‘acute axonal beading’ state, ruling out disruption of the axonal membrane, which sets this form of axon injury apart from previously described forms of traumatic and inflammatory axon damage. Morphological, pharmacological and genetic analyses showed that AQP4-IgG-induced axon injury involved osmotic stress and ionic overload, but does not appear to use canonical pathways of Wallerian-like degeneration. Subcellular analysis of beaded axons demonstrated remodeling of the axonal cytoskeleton in beaded axons, especially local loss of microtubules. Treatment with the microtubule stabilizer epothilone, a therapy in development for traumatic and degenerative axonopathies, prevented axonal beading, while destabilizing microtubules sensitized axons for beading. Our results reveal a distinct form of immune-mediated axon pathology in NMO that mechanistically differs from known cascades of posttraumatic and inflammatory axon loss, and suggest a new strategy for neuroprotection in NMO and related diseases."],["dc.identifier.doi","10.1093/brain/awac079"],["dc.identifier.pmid","35202467"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/106013"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/454"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/59"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation.eissn","1460-2156"],["dc.relation.issn","0006-8950"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.relation.workinggroup","RG Misgeld"],["dc.relation.workinggroup","RG Schifferer"],["dc.rights","CC BY-NC 4.0"],["dc.title","A new form of axonal pathology in a spinal model of neuromyelitis optica"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]