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Bladder outlet obstruction disrupts circadian bladder function in mice.

Takeya Kitta1, Hiroki Chiba2, Yukiko Kanno2

  • 1Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. kitta@fb3.so-net.ne.jp.

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Long-term partial bladder outlet obstruction (pBOO) in mice disrupts the daily circadian bladder function, leading to decreased micturition frequency. This dysfunction may involve weight gain and altered serotonin receptor 5-HT2B expression.

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Area of Science:

  • Urology
  • Chronobiology
  • Physiology

Background:

  • The circadian clock regulates daily physiological rhythms, including micturition.
  • Partial bladder outlet obstruction (pBOO) is known to cause hyperactive voiding.
  • Long-term effects of pBOO on circadian bladder function remain unclear.

Purpose of the Study:

  • To investigate the long-term impact of pBOO on circadian bladder function in mice.
  • To assess changes in micturition behavior and gene expression following chronic pBOO.

Main Methods:

  • Long-term pBOO was induced in mice by proximal urethral ligation.
  • Micturition behavior was recorded using an automated voided stain on paper method at multiple time points.
  • Quantitative gene expression analysis (qRT-PCR) was performed 24 months post-surgery.

Main Results:

  • Micturition frequency significantly decreased in pBOO mice at 3, 6, and 12 months post-surgery compared to 1 month.
  • pBOO mice showed a significant increase in body weight at 12 months compared to sham controls.
  • A 3.4-fold increase in 5-HT2B receptor mRNA expression was observed in the pBOO group.

Conclusions:

  • Long-term pBOO disrupts the circadian rhythm of bladder function in mice, mimicking human nocturia.
  • Potential contributing factors include weight gain and alterations in serotonergic pathways, specifically the 5-HT2B receptor.