Cuprizone-mediated demyelination reversibly degrades voiding behavior in mice while sparing brainstem reflex

J Neurosci Res. 2022 May 20. doi: 10.1002/jnr.25065. Online ahead of print.ABSTRACTMultiple sclerosis (MS) is a chronic, progressively debilitating demyelinating disease of the central nervous system (CNS). Nearly 80% of MS patients experience lower urinary tract dysfunction early in their diagnosis. This significantly affects the quality of life, and in latter stages of disease is a leading cause of hospitalization. Previously, animal models have shown that inflammatory demyelination in the CNS causes profound bladder dysfunction, but the confounding influence of systemic inflammation limits the potential interpretation of the contribution of CNS demyelination to bladder dysfunction. Since the micturition circuit has myelinated neuronal connections in the cortex, brainstem, and spinal cord, we examined alterations in bladder function in the cuprizone model characterized by demyelinating lesions in the cortex and corpus callosum that are independent of T-cell-mediated autoimmunity. Herein, we report that a 4-week dietary cuprizone treatment in C57Bl/6J mice induced alterations in voiding behavior with increased micturition frequency and reduced volume voided, similar to human MS bladder dysfunction. Subsequently, recovery from cuprizone treatment restored normal bladder function. Demyelination and remyelination were confirmed by Luxol Fast Blue staining of the corpus callosum. Additionally, we also determined that an 8-week cuprizone treatment, resulting in chronic demyelinat...
Source: Cell Research - Category: Cytology Authors: Source Type: research