The roles of microglia and astrocytes in phagocytosis and myelination: Insights from the cuprizone model of multiple sclerosis.

Autor: Sen MK; School of Medicine, Western Sydney University, Penrith, Australia., Mahns DA; School of Medicine, Western Sydney University, Penrith, Australia., Coorssen JR; Faculty of Applied Health Sciences and Faculty of Mathematics & Science, Brock University, St. Cathari, Canada., Shortland PJ; School of Science, Western Sydney University, Penrith, Australia.
Jazyk: angličtina
Zdroj: Glia [Glia] 2022 Jul; Vol. 70 (7), pp. 1215-1250. Date of Electronic Publication: 2022 Feb 02.
DOI: 10.1002/glia.24148
Abstrakt: In human demyelinating diseases such as multiple sclerosis (MS), an imbalance between demyelination and remyelination can trigger progressive degenerative processes. The clearance of myelin debris (phagocytosis) from the site of demyelination by microglia is critically important to achieve adequate remyelination and to slow the progression of the disease. However, how microglia phagocytose the myelin debris, and why clearance is impaired in MS, is not fully known; likewise, the role of the microglia in remyelination remains unclear. Recent studies using cuprizone (CPZ) as an animal model of central nervous system demyelination revealed that the up-regulation of signaling proteins in microglia facilitates effective phagocytosis of myelin debris. Moreover, during demyelination, protective mediators are released from activated microglia, resulting in the acceleration of remyelination in the CPZ model. In contrast, inadequate microglial activation or recruitment to the site of demyelination, and the production of toxic mediators, impairs remyelination resulting in progressive demyelination. In addition to the microglia-mediated phagocytosis, astrocytes play an important role in the phagocytic process by recruiting microglia to the site of demyelination and producing regenerative mediators. The current review is an update of these emerging findings from the CPZ animal model, discussing the roles of microglia and astrocytes in phagocytosis and myelination.
(© 2022 The Authors. GLIA published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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