Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease

Axonal degeneration determines the clinical outcome of multiple sclerosis (MS), and is thought to result from exposure of denuded axons to immune-mediated damage. We challenge this view after finding in MS and its mouse models that myelin itself increases the risk of axons to degenerate under inflammatory conditions. We propose a model for demyelinating diseases in which for axons that remain myelinated, and thus shielded from the extracellular milieu, dependence from oligodendroglial support turns fatal in an autoimmune disease environment. Overall design: CD45+ cells were isolated from the lumbosacral spinal cord white matter of C57BL/6J (WT) and hMBP mice via MACS and analysed with scRNAseq (10x technology) hMBP mice described in: https://doi.org/10.1038/s41467-020-19152-7