Background: Bladder dysfunction is an important symptom of experimental autoimmune encephalomyelitis (EAE). Our previous study showed that EAE-induced upregulation of the E-prostanoid receptor 3 (EP3) and E-prostanoid receptor 4 (EP4) in the bladder was accompanied by bladder dysfunction. Although many other studies have evaluated the lower urinary tract symptoms in multiple sclerosis, the mechanism remains unclear.
Objectives: To investigate the effects of interstitial cells of Cajal (ICC) on bladder dysfunction in a novel neurogenic bladder model induced by experimental autoimmune encephalomyelitis.
Materials and methods: The EAE model was induced by a previously established method, and bladder functions in mice were evaluated. Bladders were harvested for the analysis of ICCs and the genes associated with bladder mechanosensation including pannexin 1 (Panx1) and Gja1 (encoding connexin43) by immunofluorescence and western blotting. The stem cell factor cytokine (SCF) was intraperitoneally injected at the beginning of EAE onset.
Results: EAE mice developed profound bladder dysfunction characterized by significant urine retention, increased micturition and decreased urine output per micturition. EAE induced a significant decrease in c-Kit expression and ICCs number. EAE also induced a significant increase in pannexin 1 and connexin43. SCF treatment could ameliorate all of these pathological changes.
Conclusions: ICCs and stem cell factor play an important role in EAE-induced bladder dysfunction, which may be used as therapeutic options in treating patients with multiple sclerosis-related bladder dysfunction.
Keywords: Connexin43; Experimental autoimmune encephalomyelitis; Interstitial cells of Cajal; Neurogenic bladder; Pannexin 1.