Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Wylot B

PROVIDER: S-EPMC7017166 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Wylot Bartosz B Mieczkowski Jakub J Niedziolka Sylwia S Kaminska Bozena B Zawadzka Malgorzata M

Cells 20191231 1

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. Macrophag ...[more]

PMID: 31906095

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Dataset Information

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

Publications

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

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