English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Remyelination, a highly efficient central nervous system (CNS) regenerative process, is performed by oligodendrocyte progenitor cells (OPCs), which are recruited to the demyelination sites and differentiate into mature oligodendrocytes to form a new myelin sheath. Microglia, the specialized CNS-resident phagocytes, were shown to support remyelination through secretion of factors stimulating OPC recruitment and differentiation, and their pharmacological depletion impaired remyelination. Macrophage colony-stimulating factor (Csf1) has been implicated in the control of recruitment and polarization of microglia/macrophages in injury-induced CNS inflammation. However, it remains unclear how Csf1 regulates a glial inflammatory response to demyelination as well as axonal survival and new myelin formation. Here, we have investigated the effects of the inherent Csf1 deficiency in a murine model of remyelination. We showed that remyelination was severely impaired in Csf1-/- mutant mice despite the fact that reduction in monocyte/microglia accumulation affects neither the number of OPCs recruited to the demyelinating lesion nor their differentiation. We identified a specific inflammatory gene expression signature and found aberrant astrocyte activation in Csf1-/- mice. We conclude that Csf1-dependent microglia activity is essential for supporting the equilibrium between microglia and astrocyte pro-inflammatory vs. regenerative activation, demyelinated axons integration and, ultimately, reconstruction of damaged white matter.

Csf1 Deficiency Dysregulates Glial Responses to Demyelination and Disturbs CNS White Matter Remyelination