Montefiore Medical Center / Albert Einstein College of Medicine
Introduction: Stress caused by exposure to prolonged constant illumination (CI) has been shown to result in desquamation of superficial urothelial cells and disrupt the urothelial barrier in the mouse bladder. A leaky urothelium is a recognized factor in mechanisms that can drive bladder hypersensitivity and emergence of symptoms of urgency and urinary frequency. However, little is known of the effects of this type of stressor on bladder function. The goal of this study was to determine if exposure to constant illumination stress (CIS) alters the mouse voiding behavior, and if the effects of CIS persist after stress cessation.
Methods: Female C57BL/6CrN mice (20-weeks old) were randomly assigned to control (submitted to conventional 12h/day room illumination) or CIS (96hrs of constant room illumination) groups. Voiding behavior in the animals’ active (night-time) and sleep (daytime) phases was characterized using the voided stain of paper (VSOP) method. VSOP was conducted at baseline (pre-CIS), at the day after ending the 96hrs-CIS and at 7 and 14 days after CIS cessation. Spontaneously voided urine was collected at these time points to indirectly evaluate urothelial sensory function by quantifying changes in urine ATP levels using the luciferin-luciferase assay. Data was expressed relative to pre-CIS levels and non-stressed controls, and statistical differences determined at a p<0.05 level using the Mann-Whitney test.
Results: Exposure to 96hrs-CIS induced a 2.5-fold increase in urinary frequency of CIS-mice (pre-CIS: 0.25±0.04 voids/hour vs 96hr-CIS: 0.40±0.06 voids/hour, n=5, p<0.03). At 7- and 14-days post-CIS, the urinary frequency of CIS-mice remained 2.7- and 2.4-fold higher than that of non-stressed controls, respectively. Remarkably, this persistent effect of CIS was observed in the animals’ sleep phase (daytime) but not in their active phase (night-time), indicating development of nocturia. Further investigation showed that voided ATP levels were markedly elevated after 96hrs-CIS and remained at 2.5-fold higher levels than controls at 14 days, indicating dysregulation of urothelial mechanosensory responses.
Conclusions: Exposure to 96 hours of constant illumination causes persistent, long-lasting changes in voiding function that may be due to urothelial sensory dysfunction. The CIS model can provide a reliable and simple tool to investigate mechanisms underlying the effects of stress on urinary function.
Source of Funding: DoD-CDMRP W81XWH-21-1-0465 (PI: Suadicani)