Sleep Fragmentation Induces Urinary Dysfunction in Mice
Poster #: 115
Session/Time: B
Author:
Mariah Jensen-Wachspress, BS
Mentor:
Petra Popovics, MS, PhD
Research Type: Basic Science
Abstract
INTRODUCTION:
Benign prostatic hyperplasia (BPH) is the benign growth of the prostate gland due to the proliferation of epithelial and stromal cells in the transition zone. This enlargement can lead to urinary dysfunction, causing lower urinary tract symptoms (LUTS). The most bothersome symptom is nocturia, or getting up at night to urinate, which results in sleep fragmentation (SF). SF has been found to worsen inflammation after stroke and in cardiovascular disease, leading us to speculate that SF may also contribute to inflammation and subsequent urinary dysfunction in BPH. This project utilized a mouse model of sleep fragmentation to test this hypothesis.
METHODS:
C57BL/6J mice were housed in a SF chamber for twelve weeks. During their sleep period, from 6am-6pm, an automated bar moved across the bottom of the chamber to interrupt their sleep. Activity control mice had the bar moving from 6pm-6am whereas another group of control mice were kept in normal cages. Every second week, the mice underwent a void spot assay (VSA), where they were individually housed for 4 hours in a cage fitted with filter paper. Filter papers were imaged with a ChemiDoc station and analyzed with Void Whizzard to observe changes in urination. After the 12-week experiment, the mice were euthanized, and the bladder and prostate lobes were weighed, fixed, and embedded in FFPE. Inflammation was determined with CD45 immunohistochemistry, and images were analyzed by counting CD45+ cells normalized to tissue area. Groups were compared using one-way ANOVA or the nonparametric equivalent.
RESULTS:
After 12-weeks, bladder weights were significantly increased in the SF group (15% increase, p=0.012) compared with controls. VSA showed that, at week 12, there was a significant decrease in both voiding volume (1.8-fold decrease, p=0.0328) and void count (2-fold decrease, p=0.0498) in the SF group compared with controls. CD45+ cell count was not significantly changed in the SF group compared with controls.
DISCUSSION:
The increase in bladder weights with the decrease in voiding volume and count points towards hypertrophy of the bladder caused by bladder outlet obstruction. These results suggest that SF may exacerbate LUTS. Though CD45 count was not significantly changed in the prostate lobes, further work will include determining immune cell types and fibrosis. Understanding this relationship could reveal a new driver causing or worsening BPH/LUTS.
Benign prostatic hyperplasia (BPH) is the benign growth of the prostate gland due to the proliferation of epithelial and stromal cells in the transition zone. This enlargement can lead to urinary dysfunction, causing lower urinary tract symptoms (LUTS). The most bothersome symptom is nocturia, or getting up at night to urinate, which results in sleep fragmentation (SF). SF has been found to worsen inflammation after stroke and in cardiovascular disease, leading us to speculate that SF may also contribute to inflammation and subsequent urinary dysfunction in BPH. This project utilized a mouse model of sleep fragmentation to test this hypothesis.
METHODS:
C57BL/6J mice were housed in a SF chamber for twelve weeks. During their sleep period, from 6am-6pm, an automated bar moved across the bottom of the chamber to interrupt their sleep. Activity control mice had the bar moving from 6pm-6am whereas another group of control mice were kept in normal cages. Every second week, the mice underwent a void spot assay (VSA), where they were individually housed for 4 hours in a cage fitted with filter paper. Filter papers were imaged with a ChemiDoc station and analyzed with Void Whizzard to observe changes in urination. After the 12-week experiment, the mice were euthanized, and the bladder and prostate lobes were weighed, fixed, and embedded in FFPE. Inflammation was determined with CD45 immunohistochemistry, and images were analyzed by counting CD45+ cells normalized to tissue area. Groups were compared using one-way ANOVA or the nonparametric equivalent.
RESULTS:
After 12-weeks, bladder weights were significantly increased in the SF group (15% increase, p=0.012) compared with controls. VSA showed that, at week 12, there was a significant decrease in both voiding volume (1.8-fold decrease, p=0.0328) and void count (2-fold decrease, p=0.0498) in the SF group compared with controls. CD45+ cell count was not significantly changed in the SF group compared with controls.
DISCUSSION:
The increase in bladder weights with the decrease in voiding volume and count points towards hypertrophy of the bladder caused by bladder outlet obstruction. These results suggest that SF may exacerbate LUTS. Though CD45 count was not significantly changed in the prostate lobes, further work will include determining immune cell types and fibrosis. Understanding this relationship could reveal a new driver causing or worsening BPH/LUTS.