Early life voiding dysfunction leads to lower urinary tract dysfunction through alteration of muscarinic and purinergic signaling in the bladder

Lower urinary tract dysfunction (LUTD) is a common problem in children and constitutes up to 40 percent of pediatric urology clinic visits. Improved diagnosis and interventions have been leading to better outcomes in many patients, while some children are left untreated or do not respond to the treatment successfully. In addition, many of these patients are lost by the pediatric urologists during their teenage years, and the outcome in later life largely remains unidentified. Studies suggest childhood LUTD is associated with subsequent adult urinary tract symptoms. However, whether and how early life LUTD attributes to urinary symptoms in those patients later in life remains to be elucidated. In the current study, we investigated the effects of early life voiding perturbation on bladder function using a neonatal maternal separation (NMS) protocol in mice. NMS group displayed a delayed development of voluntary voiding behavior, a significant reduction of functional bladder capacity, and bladder overactivity compared to control mice later in life. In vitro evaluation of detrusor smooth muscle and molecular study showed a decrease in muscarinic alongside an increase in purinergic contribution in detrusor contractility in NMS mice compared to control group. These results suggest that early life bladder dysfunction interfered with the normal maturation of the voluntary micturition control and facilitated LUTD in later stage, which is at least partly attributed to an alteration of muscarinic and purinergic signaling in the urinary bladder.

American journal of physiology. Renal physiology. 2018 Aug 08 [Epub ahead of print]

Nao Iguchi, Anna P Malykhina, Duncan T Wilcox

Urology, University of Colorado., Division of Urology, Department of Surgery, University of Colorado Denver, United States., Division of Urology, Department of Surgery, University of Colorado School of Medicine and Children's Hospital Colorado, United States.