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1 Acta Neurobiologiae Experimentalis

1 2011

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Reduction of microglia response affects oligodendrocyte precursor cell differentiation in a model of demyelination/remyelination

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Wylot B. , Sielska M. , Kaminska B. , Zawadzka M.

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Remyelination in the CNS is a regenerative process carried by oligodendrocyte precursor cells (OPC), which are recruited to the demyelination site and differentiate into mature oligodendrocytes to form a new myelin sheath. Macrophages were shown to support remyelination through myelin debris clearance as well as secretion of chemokines and growth factors stimulating OPC recruitment and differentiation. Moreover, several in vivo studies demonstrated that pharmacological macrophage depletion may impair remyelination. The role of macrophages in new myelin formation is not fully understood and the involvement of these cells in remyelination process has not yet been studied in a model of inherent macrophage reduction. Osteopetrotic (op/op) mice have a mutation in CSF1 gene leading to reduction in monocytes as well as microglia number. Therefore, they make a good model for studying the role of central- and peripheral-derived macrophages in regenerative processes of the CNS. The aim of the present study was to examine the influence of reduction in macrophages in op/op mice on remyelination process in a model of focal demyelination of the spinal cord. Osteopetrotic mice were injected with myelin toxin into the ventral and dorsal funiculus of the spinal cord to induce focal demyelination. Toluidine blue staining of semi-thin resin sections at 28 days post lesion (dpl) revealed impaired remyelination in op/ op mice with the presence of extensive non-remyelinated areas in the lesion. Immunostaining of sections from op/op mice at 10 dpl showed severely reduced activity of macrophages at the lesion site as compared to control. OPC number in the lesions from op/op mice was not affected. Results of the present study provide further evidence for a crucial role of macrophages in supporting CNS remyelination. They also confirm usefulness of op/op mice as a model for remyelination studies.