Reduction in Bladder Volume Alters Expression of Hypocretin/Orexin Receptors in Brain Stem in Rats: a Correlation With Sleep Architecture

Abstract

Purpose Our recent study revealed that enuretic children have more light sleep associated with frequent cortical arousals. The neurons of the lateral hypothalamic and perifornical areas that express Hypocretin/Orexin(Hcrt/Orx) have been implicated in control of sleep- wake cycle and CNS arousal mechanisms. We therefore propose to use an animal model to evaluate brain functional changes in response to bladder dysfunction. Material and Methods Twenty four adult male New Zealand Wistar rats were used. Animals underwent either surgical reduction of bladder volume (RBV, n = 12) or SHAM operation (n = 12). Animals were kept in metabolic cages for noninvasive monitoring of voiding patterns. Radiotelemeters were implanted in both groups after 4 weeks of recovery and electroencephalogram was recorded via readiotelemetric probes. On completion, animals were anesthetized and brain samples harvested. Serial cryostat sections of brain were obtained throughout the hypothalamus and the sections were immunostained for Hcrt -1. Results Voided volume significantly reduced and voiding frequency increased in RBV group. Our results demonstrated impaired sleep architecture in animals with reduced bladder volume. Light non-rapid eye movement sleep occurred more and deep and rapid eye movement sleep occurred significantly less RBV group (59.2% vs 35.6%, p Conclusions An alteration in sleep architecture occurred in response to surgical reduction of bladder volume in rats. Enhancement of arousal accompanied by marked reduction in paradoxical sleep and deep slow wave sleep correlated with significant increase in Hcrt/Orx cells in RBV group, suggesting the existence of a dialogue of dysfunctional bladder and CNS.