Abbreviations & Acronyms AMPA = a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid BOO = bladder outlet obstruction BPH = benign prostatic hyperplasia DO = detrusor overactivity HIF-1 = hypoxia-inducible factor-1 IL = interleukin LUTS = lower urinary tract symptoms NGF = nerve growth factor NO = nitric oxide NVC = non-voiding contraction OAB = overactive bladder pBOO = partial bladder outlet obstruction TGF-b = transforming growth factor-b Abstract: The functions of the lower urinary tract have been investigated for more than a century. Lower urinary tract symptoms, such as incomplete bladder emptying, weak urine stream, daytime urinary frequency, urgency, urge incontinence and nocturia after partial bladder outlet obstruction, is a frequent cause of benign prostatic hyperplasia in aging men. However, the pathophysiological mechanisms have not been fully elucidated. The use of animal models is absolutely imperative for understanding the pathophysiological processes involved in bladder dysfunction. Surgical induction has been used to study lower urinary tract functions of numerous animal species, such as pig, dog, rabbit, guinea pig, rat and mouse, of both sexes. Several morphological and functional modifications under partial bladder outlet obstruction have not only been observed in the bladder, but also in the central nervous system. Understanding the changes of the lower urinary tract functions induced by partial bladder outlet obstruction would also contribute to appropriate drug development for treating these pathophysiological conditions. In the present review, we discuss techniques for creating partial bladder outlet obstruction, the characteristics of several species, as well as issues of each model, and their translational value.

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Apart from increased stress urinary incontinence, there was an improvement in overall urinary function in terms of patient-reported symptoms and urodynamics, despite deep vesicovaginal space dissection. Hence, LSC is a viable surgical option for pelvic organ prolapse, restoring both level 1 and level 2 support without detrimental effects on urinary function.

the circadian clock programs daily rhythms and coordinates multiple behavioural processes, including micturition. partial bladder outlet obstruction (pBoo) in mice produces hyperactive voiding. However, long-term effects of pBOO on bladder function have not been clarified. In this study, we investigated micturition under conditions of impaired circadian bladder function by inducing long-term pBoo by tying the proximal urethra. Micturition behavior was evaluated at 1, 3, 6 and 12 months after surgery. We used automated voided stain on paper method for a precise micturition recording for mice. And quantitative assessment of gene expression was performed at 24 months after pBOO surgery using qRT-PCR procedure. The micturition frequencies in the pBOO group were significantly decreased at 3, 6, and 12 months compared to those at 1 month after operation in the same group (p < 0.05). Body weight of pBOO mice was significantly increased compared to sham operated mice at 12 months. The expression level of mRNA was exhibited a 3.4-fold nominal increased for a 5-HT2B receptor in the pBoo group compared to the sham group. the current study found that long-term pBoo led to disruption of the circadian bladder function (the day/night cycle) in mice, similar to those observed in human as nocturia. this disruption is possible involvement of the gain of body weight and/or serotonergic alteration after pBoo. Abbreviations BOO Bladder outlet obstruction pBOO Partial bladder outlet obstruction LUTS Lower urinary tract symptoms aVSOP Automated voided stain on paper Mets Metabolic syndrome CRF Corticotropin-releasing factor HPA Hypothalamus-pituitary-adrenal α1ARs α1-Adrenergic receptors In men as a result of benign prostatic enlargement bladder outlet obstruction (BOO) is one of the most common causes of lower urinary tract symptoms (LUTS). Partial BOO (pBOO) significantly alters bladder morphology and function. Clinically, benign prostatic hyperplasia, bladder neck sclerosis, urethral valves or urethral strictures can cause mechanical BOO 1. Although a correlation between LUTS and BOO or metabolic syndrome are known, to our knowledge, the detailed aetiology of LUTS remains unknown. Some symptoms, e.g. nocturia, remain to treat completely due to unclear mechanisms of LUTS. Several studies have shown that nocturia is a common complaint and (one of) the most frequent events in male LUTS. Nocturnal voiding disrupts sleep, and therefore repeated nocturnal voiding deteriorates the health-related quality of life 2. There is very little information about the micturition behaviour as circadian bladder function in animal model. Previous studies have shown that pBOO induces non-voiding contraction and shortening of inter-contraction interval in urinary bladder in animals 3,4. Furthermore, pBOO leads to several morphological and functional changes in afferent pathways as well as in the bladder. To empty partial obstructed-bladder, pBOO produces compensate hypertrophy of detrusor, which causes gain of the thickness and weight of the bladder wall ...

Aims/Methods: To investigate whether smoking affects the serum level of leptin, 708 male workers aged 25–65 years old were cross-sectionally surveyed. Results: Multiple regression analysis indicated that among the various parameters examined, the level of leptin was positively associated with the body mass index and the levels of insulin, total cholesterol and uric acid, and was inversely associated with physical activity and the level of creatinine. The partial correlation coefficient of leptin was highest against the body mass index (r = 0.40), followed by insulin (0.29) and physical activity (–0.14), after adjustment for other leptin-related variables. However, no association was observed between the level of leptin and smoking (0.05), alcohol consumption (0.09) or age (0.09). Conclusions: The findings suggest that among life-style habits, physical activity, but not smoking or alcohol consumption, significantly affects the serum level of leptin in Japanese men.

Aims: The serotonin (5-HT2c) receptor is known to be involved in the mechanism of urethral closure in a model of stress incontinence. Lorcaserin (Belviq®) has received Food and Drug Administration approval for the treatment of obesity.However, it is unclear whether this selective 5-HT2c receptor agonist enhances urethral closure in stress urinary incontinence (SUI) models. Therefore, we investigated whether lorcaserin could enhance urethral closure in female rats with vaginal distention (VD). Methods: Normal female rats and rats with stress incontinence induced by VD were tested. We evaluated the effect of a single dose of lorcaserin (0.03, 0.3, or 0.9 mg/kg with cumulative administration) on the urethral pressure amplitude during electrical stimulation (A-URE) and on the urethral baseline pressure (UBP). The manual compression-induced leak point pressure (LPP) was also measured. Results: In VD rats, a single intravenous injection of lorcaserin (0.3 and 0.9 mg/kg) significantly increased both A-URE and LPP compared to saline (P < 0.05). In normal rats, intravenous lorcaserin (0.3 and 0.9 mg/kg) also significantly increased A-URE and LPP compared to saline (P < 0.05). The changes of A-URE and LPP, which are parameters of active urethral closure, were significantly larger in normal rats than in VD rats. Conclusions: We showed that lorcaserin can activate the external urethral sphincter and pelvic floor muscles, suggesting an influence on active closure mechanisms. 5-HT2c receptors agonists may have dual effects in patients with SUI, not only by reducing obesity but also by enhancing active urethral closure. K E Y W O R D S5-HT2c receptor agonist, active urethral closure mechanism, lorcaserin, stress urinary incontinenceThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Although Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and subsequent motor symptoms, various non-motor symptoms often precede these other symptoms. While motor symptoms are certainly burdensome, a wide range of non-motor symptoms have emerged as the key determinant of the quality of life in PD patients. The prevalence of lower urinary tract symptoms differs according to the study, with ranges between 27% and 63.9%. These can be influenced by the stage of disease, the presence of lower urinary tract-related comorbidities, and parallels with other manifestations of autonomic dysfunction. Animal models can provide a platform for investigating the mechanisms of PD-related dysfunction and for the assessment of novel treatment strategies. Animal research efforts have been primarily focused on PD motor signs and symptoms. However, the etiology of lower urinary tract dysfunction in PD has yet to be definitively clarified. Several animal PD models are available, each of which has a different effect on the autonomic nervous system. In this article, we review the various lower urinary tract dysfunction animal PD models. We additionally discuss techniques for determining the appropriate model for evaluating the development of lower urinary tract dysfunction treatments.

Aims Urinary incontinence is prevalent among patients with Parkinson's disease (PD). In the present study, we investigated urethral functions in a rat model of PD induced by 6‐hydroxydopamine injection at their substantia nigra pars compacta as well as the roles of selective agonists/antagonist of dopamine D1‐ and D2‐like receptors in active urethral closure mechanisms. Methods We measured changes in the urethral pressure amplitude during electrical stimulation, urethral baseline pressure, and leak point pressure after intravenous administration of selective agonists or antagonists of the dopamine D1‐ and D2‐like receptors in a rat model of PD. Results The mean leak point pressure and the mean active urethral response values were significantly smaller for the untreated PD rat group compared with the control group. In PD model, the active urethral response increased significantly after treatment with the dopamine D1‐like receptor agonist, whereas that induced by the dopamine D2‐like receptor agonist decreased significantly. The response to the D2‐like receptor agonist was suppressed in the PD rat by the dopamine D2‐like receptor antagonist. Conclusion Our results suggest that the active urethral closure mechanisms are significantly impaired when dopamine is depleted. In the PD rat, dopamine D1‐like receptor activity on the central nervous system appear to partially compensate for urethral functions negatively impacted by the lack of dopamine, whereas dopamine D2‐like receptor activity might exacerbate urinary leakage owing to the negative effect of this activated receptor on urethral pressure under increased intra‐abdominal pressure.