Myelin-Remodeling in vivo: Eine Längsschnittstudie zur gezielten Myelinisierung und neuronalen Kontrolle der spärlichen Myelinisierung in der Mausrinde
Zusammenfassung der Projektergebnisse
Myelin enables fast impulse propagation and provides metabolic support of the underlying axons. The complex and diverse patterns of myelin, found along cortical axons, offer immense potential for plasticity that was shown to be associated with higher brain functions. The importance of the cortical myelin pattern stability becomes critical in demyelinating lesions, widespread in Multiple Sclerosis patients, where incomplete remyelination is associated with neurological deficits. We show that the loss of a single cortical oligodendrocyte (OL) triggers a remarkable local response during which newly matured OLs replace the original cell in a homeostatic fashion. These new OLs then restore around 70 percent of the original myelin sheaths, with a strong bias toward axons that originally were continuously myelinated. At the same time, axons in the surrounding area receive de novo myelination, mainly as patchy internodes, approximating the original amount of myelin in this cortical area. These findings show that in non-inflammatory conditions the system is capable to sense the loss of a single oligodendrocyte in adult cortex and illicit extensive remyelination. This results provide a key insight with implications for disabling demyelinating diseases of the central nervous system with poor remyelination efficiency.
Projektbezogene Publikationen (Auswahl)
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Myelin replacement triggered by single-cell demyelination in mouse cortex. Nature Communications, 11(1).
Snaidero, Nicolas; Schifferer, Martina; Mezydlo, Aleksandra; Zalc, Bernard; Kerschensteiner, Martin & Misgeld, Thomas
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Niwaki Instead of Random Forests: Targeted Serial Sectioning Scanning Electron Microscopy With Reimaging Capabilities for Exploring Central Nervous System Cell Biology and Pathology. Frontiers in Neuroanatomy, 15.
Schifferer, Martina; Snaidero, Nicolas; Djannatian, Minou; Kerschensteiner, Martin & Misgeld, Thomas
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Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation. Nature Neuroscience, 24(3), 355-367.
Jafari, Mehrnoosh; Schumacher, Adrian-Minh; Snaidero, Nicolas; Ullrich, Gavilanes Emily M.; Neziraj, Tradite; Kocsis-Jutka, Virág; Engels, Daniel; Jürgens, Tanja; Wagner, Ingrid; Weidinger, Juan Daniel Flórez; Schmidt, Stephanie S.; Beltrán, Eduardo; Hagan, Nellwyn; Woodworth, Lisa; Ofengeim, Dimitry; Gans, Joseph; Wolf, Fred; Kreutzfeldt, Mario; Portugues, Ruben ... & Kerschensteiner, Martin
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A new form of axonal pathology in a spinal model of neuromyelitis optica. Brain, 145(5), 1726-1742.
Herwerth, Marina; Kenet, Selin; Schifferer, Martina; Winkler, Anne; Weber, Melanie; Snaidero, Nicolas; Wang, Mengzhe; Lohrberg, Melanie; Bennett, Jeffrey L.; Stadelmann, Christine; Hemmer, Bernhard & Misgeld, Thomas
