Recovery from cuprizone induced incontinence is not dependent upon remyelination

Dysfunction in bladder control (incontinence) is a significant comorbidity in multiple sclerosis that diminishes patients' quality of life and is a leading cause of hospitalization. Recent evidence indicates that CNS demyelination is sufficient to induce incontinence, while bladder control is also restored following remyelination. Based on this strong association, we hypothesized that remyelination is necessary for the restoration of bladder function control after acute demyelination. To test this, we evaluated changes in bladder function in mice in which Myelin regulatory factor (Myrf) was conditionally knocked out in oligodendrocyte precursor cells (OPC)(PDGFR⍺- CreER^TM, Myrf^fl/fl (Myrf-cKO)) and compared these with control groups during and after being subjected to cuprizone treatment. Here, we report that acute demyelination leads to bladder control dysfunction which was evidenced by significantly increased voiding behavior irrespective of genotype. However, during the remyelination phase, we observed an amelioration of incontinence in all groups, including mice in which remyelination fails (e.g. Myrf-cKO mice). These data suggest that while active demyelination can initiate loss of bladder function control, failed remyelination is not an impediment to potential adaptive changes which may facilitate restoration of proper bladder function.