PhD Scientific Days 2023

Translational Medicine II.

Investigation of bladder overactivity in a novel mouse model

Text of the abstract

Introduction: Overactive bladder syndrome (OAB) affects 17% of the European population, still its medical treatment has not yet been entirely resolved. The currently available animal models of OAB are often established by using suprapubic catheterization, in this way disrupting the bladder smooth muscle’s integrity.
Aims: Our aim was to set up a novel animal model mimicking the symptoms of OAB, which could contribute to finding potentially more specific pharmacological targets for treating bladder dysfunctions.
Methods: Experiments were performed on 90-120 days old, female, C57Bl/6 mice with applying transurethral catheterization under isoflurane anesthesia. For control (CTRL) experiments, the bladders were filled with 0.9% saline solution while measuring intravesical pressure changes. Following the control experiments, a group of mice was treated intravesically with 0.5% hydrogen-peroxide (H2O2) solution (30 min) and cystometric measurements were performed after 3h and 24h. Another group was treated with i.p. cyclophosphamide (CYP) solution (200mg/kg) and cystometry was performed 24h following treatment.
Results: We found that the amplitude of non-voiding contractions (NVC) elevated significantly following H2O2-(3h and 24h) and CYP-treatment. The frequency of NVCs reduced as a result of CYP-treatment but remained unaltered after H2O2-administration. Frequency of the voiding contractions (VC) also increased significantly following either treatment compared to CTRL, whereas the amplitude of VCs did not change. Furthermore, following H2O2- and CYP-treatment, the first VC and micturition appeared at significantly lower intravesical volumes compared to CTRL measurements.
Conclusion: We successfully set up a novel mouse model for OAB using transurethral catheterization allowing us to investigate bladder function with undisturbed integrity of the detrusor muscle layer. With either H2O2- or CYP-administration, the mice produced OAB-like symptoms, shown by the increase in the amplitude of NVCs, and the frequency of VCs. Furthermore, VCs and the first micturition appeared at lower volumes as a result of treatment, indicating bladder overactivity. In summary, these mouse models may aid the identification of novel, more specific therapeutic targets for treating overactive bladder.
Funding: NKFIH K-125174, K-135683 and K-139230 and EFOP-3.6.3-VEKOP-16-2017-00009 grants.