Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis

Cunha, Maria Ines; Su, Minhui; Cantuti-Castelvetri, Ludovico; Müller, Stephan A.; Schifferer, Martina; Djannatian, Minou; Alexopoulos, Ioannis; Meer, Franziska van der; Winkler, Anne; Ham, Tjakko J. van; Schmid, Bettina; Lichtenthaler, Stefan F.; Stadelmann, Christine und Simons, Mikael (2020): Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis. In: Journal of Experimental Medicine, Bd. 217, Nr. 5, e20191390

Abstract

Remyelination requires innate immune system function, but how exactly microglia and macrophages clear myelin debris after injury and tailor a specific regenerative response is unclear. Here, we asked whether pro-inflammatory microglial/macrophage activation is required for this process. We established a novel toxin-based spinal cord model of de- and remyelination in zebrafish and showed that pro-inflammatory NF-kappa B-dependent activation in phagocytes occurs rapidly after myelin injury. We found that the pro-inflammatory response depends on myeloid differentiation primary response 88 (MyD88). MyD88-deficient mice and zebrafish were not only impaired in the degradation of myelin debris, but also in initiating the generation of new oligodendrocytes for myelin repair. We identified reduced generation of TNF-alpha in lesions of MyD88-deficient animals, a pro-inflammatory molecule that was able to induce the generation of new premyelinating oligodendrocytes. Our study shows that pro-inflammatory phagocytic signaling is required for myelin debris degradation, for inflammation resolution, and for initiating the generation of new oligodendrocytes.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0022-1007
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198