Microglia activation and regulation of remyelination in the central nervous system

by Minhui Su
Doctoral thesis
Date of Examination:2018-11-27
Date of issue:2019-08-21
Advisor:Prof. Dr. Mikael Simons
Referee:Prof. Dr. Blanche Schwappach
Referee:Prof. Dr. Steven Johnsen
Referee:Prof. Dr. André Fisher
Referee:Prof. Dr. Dr. Hannelore Ehrenreich
Referee:Prof. Dr. Tiago Fleming Outeiro
Persistent Address: http://dx.doi.org/10.53846/goediss-7399

 

 

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Abstract

English

In the central nervous system, remyelination requires the proliferation and migration of oligodendrocyte progenitor cells (OPCs) to the lesions, and the differentiation of OPCs into oligodendrocytes that remyelinate the axons. Microglia / macrophages remove damaged myelin from the lesions, mediate inflammation, and secrete cytokines and growth factors that regulate OPC responses for remyelination. In the mice deficient of MyD88 adaptor for inflammatory signaling, the recruitment of OPCs and remyelination were impaired after lysolecithin-induced focal demyelination. The lack of MyD88 signaling and defective phagosome maturation may impair the clearance of internalized myelin debris and the activation of microglia to support remyelination. Transcriptomic and proteomic analyses of demyelinated lesions and cultured microglia identified candidate molecules and pathways relevant to remyelination. Lysolecithin or autoimmune-mediated demyelination models in organotypic hippocampal slice culture provide ex vivo methods for understanding the mechanisms of demyelination and remyelination, and for evaluating the effects of candidate molecules on OPC proliferation, differentiation and myelination. In addition, MyD88 signaling is necessary for the recruitment of OPCs during remyelination in the adult CNS but may not be essential for developmental myelination.
Keywords: remyelination; microglia
 
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