microglia

insulin

axonal

metabolic syndrome

syringae

axon regeneration

ophthalmic

autoimmune encephalomyelitis

retinal_111422

simulation-based

remyelination

myelination

oecs

spectrometry_51282

experimental autoimmune encephalomyelitis

electrochemical impedance

regionalization

lingo

schwann cell

speech_121102

eLife

Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises to restore lost function, it remains unclear whether remyelination will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss in the experimental autoimmune encephalomyelitis (EAE) mouse model and evidence for remyelination in this model is complicated by ongoing inflammation, degeneration and possible remyelination. Demonstrating the functional significance of remyelination necessitates selectively altering the timing of remyelination relative to inflammation and degeneration. We demonstrate accelerated remyelination after EAE induction by direct lineage analysis and hypothesize that newly formed myelin remains stable at the height of inflammation due in part to the absence of MOG expression in immature myelin. Oligodendroglial-specific genetic ablation of the M1 muscarinic receptor, a potent negative regulator of oligodendrocyte differentiation and myelination, results in accelerated remyelination, preventing axonal loss and improving functional recovery. Together our findings demonstrate that accelerated remyelination supports axonal integrity and neuronal function after inflammatory demyelination.

Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery