2008 Annual Meeting Abstracts
Sociobiology - Social Stress Induced Dysfunctional Voiding Leads to Murine Bladder Wall Hypertrophy
Stephen A Zderic, Stephan Butler*, Joanna Sliwoski*, Michael Carr, Aileen Schast, Rita Valentino*
Children's Hospital of Philadelphia, Philadelphia, PA
Introduction: Dysfunctional voiding (DV) represents one of the most common reasons pediatric urologists are consulted and its pharmacologic management is limited by lack of an animal model. We set out to characterize the response of the murine bladder to social stress.
Methods: C57 retired breeder male mice served as aggressors. Litters of 6 week old FVB males were randomized to either single housing, or were stressed by repeat cycles of a 1 hour exposure to the larger C57 mouse followed by a 23 hour period of barrier separation over 4 weeks. Voiding patterns were determined and at sacrifice, body and bladder weights were measured. RNA and nuclear protein fractions were isolated from each bladder. Gel shift assays were performed using fluorescent labeled DNA probes for the transcription factors NFAT and MEF-2. RT-PCR was used to determine the expression of myosin heavy chain (MHC) B and A mRNA isoforms with normalization to 18S RNA. Comparisons between the control and stress groups were made using t-tests.
Results:
| Control | Stress | P Value |
| Bladder mass/body weight | 0.62 ± 0.1 | 1.59 ± 0.58 | < 0.001 |
| Voids/12 hours | 9.8 ± 4 | 2.9 ± 1.1 | < 0.01 |
| Average void volume | 0.06 ± 0.02 | 0.37 ± 0.1 | < 0.01 |
| NFAT | 54.6 ± 25 | 138.4 ± 42 | < 0.02 |
| MEF-2 | 7.5 ± 4.8 | 24.1 ± 8.9 | < 0.02 |
| MHC B | 0.56 ± 0.1 | 1.03 ± 0.34 | < 0.02 |
| MHC A | 0.27 ± 0.03 | 0.36 ± 0.08 | < 0.05 |
Conclusions: Stressed FVB mice developed altered voiding patterns, bladder wall hypertrophy, and increased nuclear expression of the transcription factors NFAT and MEF-2 as well as increased expression of MHC isoforms. These molecular findings are also observed following anatomic outlet obstruction. We conclude that with social stress, urinary retention develops resulting in bladder wall hypertrophy making this a model of DV.
