Effects of Experimental Autoimmune Encephalomyelitis on Bladder Function and Properties of Pelvic Ganglion Neurons

ABSTRACT Multiple sclerosis (MS) has substantial impacts on autonomic function. In part, MS results in loss of normal autonomic activity that contributes to disease-associated pathology such as neurogenic bladder, bowel, and sexual dysfunction. Yet little is known of the impacts of MS on peripheral autonomic neurons that directly innervate these target organs. In this study, we measured changes in properties of neurons of the mouse major pelvic ganglion (MPG) associated with two different levels of severity in mice with experimental autoimmune encephalomyelitis (EAE), a model of MS. Our data show that bladder function and physiological properties of MPG neurons are altered in association with EAE, and differ between less and more severe clinical scores associated with disease progression. EAE results in decreased bladder function measured by decreased urine output and increased micturition pressures. In the most severely affected animals, action potentials (APs) in MPG neurons show increased half-widths as a result of decreased maximum decay slopes leading to overall broader and longer APs and lower maximum firing frequency. These changes in AP properties are associated with differences in ion channel subunit expression as well. KCNA1-4, KCNN3 and SCN2A1 and SCN3A mRNA levels in MPGs decreased with disease severity. Taken together, our data indicate that peripheral autonomic neurons are fundamentally altered in EAE, suggesting that longer-term therapeutic approaches for MS could target these neurons directly to potentially help ameliorate neurogenic target organ dysfunction.