A Novel Mouse Model of Chronic Inflammatory and Overactive Bladder by a Single Intravesical Injection of Hydrogen Peroxide

Homan, Takashi; Tsuzuki, Tetsunori; Dogishi, Koji; Shirakawa, Hisashi; Oyama, Tatsuya; Nakagawa, Takayuki; Kaneko, Shuji

doi:10.1254/jphs.12265fp

Cited by 31 publications

(56 citation statements)

References 57 publications

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“…Previous reports have demonstrated that OAB may be caused by chronic inflammation (51,52) and proteins related with inflammation can be served as biomarker for OAB syndrome (53). In addition, modulating inflammatory response with anti-inflammation drugs can improve the detrusor contraction disorder (54,55).…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction

Park

Lim

Kim

et al. 2018

Molecular & Cellular Proteomics

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SummaryOveractive bladder (OAB) syndrome is a condition that has four symptoms: urgency, urinary frequency, nocturia, and urge incontinence and negatively affects a patient's life. Recently, it is considered that the urinary bladder urothelium is closely linked to pathogenesis of OAB. However, the mechanisms of pathogenesis of OAB at the molecular level remain poorly understood, mainly as a result of lack of modern molecular analysis. The goal of this study is to identify a potential target protein that could act as a predictive factor for effective diagnosis and aid in the development of therapeutic strategies for the treatment of OAB syndrome. We produced OAB in a rat model and performed the first proteomic analysis on the mucosal layer (urothelium) of the bladders of sham control and OAB rats. The resulting data revealed the differential expression of 355 proteins in the bladder urothelium of OAB rats compared to sham subjects. Signaling pathway analysis revealed that the differentially expressed proteins were mainly involved in the inflammatory response and apoptosis.Our findings suggest a new target for accurate diagnosis of OAB that can provide essential information for the development of drug treatment strategies as well as establish criteria for screening patients in the clinical environment.

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Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction

Park

Lim

Kim

et al. 2018

Molecular & Cellular Proteomics

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“…Previous studies (19,20,21,33,39) have demonstrated that urinary bladder NGF expression is increased with increased voiding frequency. Given that voiding frequency increased in mice exposed to stress but decreased in mice exposed to increased stress, we hypothesized that NGF expression would be selectively increased in the bladders of stressed mice.…”

Section: Effects Of Social Stress On Ngf and Histamine Protein Expresmentioning

confidence: 96%

“…can affect the micturition reflex pathway (13,19,20,21,28,33,35,36). In addition, inflammation induced by noxious chemical or mechanical stimulation in the urinary bladder of rodents increases the expression of NGF mRNA as well as protein throughout the bladder, causing morphological changes in both bladder sensory and motor neurons (6,23,39,40).…”

Section: R896 Social Stress Induction Of Bladder Dysfunctionmentioning

confidence: 99%

“…Animal models based on intravesical instillation of inflammatory agents or surgical ligations of the bladder outlet have recently been created to study overactive bladder (20,31). However, these models are less effective in mirroring human bladder function disorders in children than in adults and have limited validity in studies of stress-related bladder dysfunction.…”

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confidence: 99%

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Social stress induces changes in urinary bladder function, bladder NGF content, and generalized bladder inflammation in mice

Mingin

Peterson

Erickson

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Social stress may play a role in urinary bladder dysfunction in humans, but the underlying mechanisms are unknown. In the present study, we explored changes in bladder function caused by social stress using mouse models of stress and increasing stress. In the stress paradigm, individual submissive FVB mice were exposed to C57BL/6 aggressor mice directly/indirectly for 1 h/day for 2 or 4 wk. Increased stress was induced by continuous, direct/indirect exposure of FVB mice to aggressor mice for 2 wk. Stressed FVB mice exhibited nonvoiding bladder contractions and a decrease in both micturition interval (increased voiding frequency) and bladder capacity compared with control animals. ELISAs demonstrated a significant increase in histamine protein expression with no change in nerve growth factor protein expression in the urinary bladder compared with controls. Unlike stressed mice, mice exposed to an increased stress paradigm exhibited increased bladder capacities and intermicturition intervals (decreased voiding frequency). Both histamine and nerve growth factor protein expression were significantly increased with increased stress compared with control bladders. The change in bladder function from increased voiding frequency to decreased voiding frequency with increased stress intensity suggests that changes in social stress-induced urinary bladder dysfunction are context and duration dependent. In addition, changes in the bladder inflammatory milieu with social stress may be important contributors to changes in urinary bladder function.

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“…Also in rats, Homan et al [23] observed that a single intravesical injection of H 2 O 2 significantly increased the number of voids, which lasted up to 7 days. The effects of H 2 O 2 are significantly diminished by antioxidants such as dimethylthiourea or deferoxamine, indicating that those effects are ROS-mediated [22] .…”

Section: Aging Oxidative Stress and Inflammationmentioning

confidence: 96%

Lower Urinary Tract Symptoms and Aging: The Impact of Chronic Bladder Ischemia on Overactive Bladder Syndrome

Camões

Coelho²,

Castro-Díaz

et al. 2015

Urol Int

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Introduction: The overactive bladder syndrome (OAB) is one of the most common and bothersome subsets of lower urinary tract symptoms (LUTS), affecting predominantly the aged population, with a worldwide distribution. This syndrome has not been completely understood, yet the aging process and the decreased blood flow to the bladder have been highlighted as closely related to this phenomenon. Materials and Methods: We performed a search on the online database PubMed/MEDLINE with the following MESH terms: ‘Overactive Bladder AND (Ischemia OR Aging OR Vascular Disease)'. We considered manuscripts written in English and published in the last 10 years (2004-2014, October). Additional manuscripts, such as referenced by reviews, were further included. Results: The aging process and the structural and functional changes resulting from an ischemic process emerge as important features that contribute to OAB. The ischemic-induced molecular and structural modifications that occur in the bladder have only recently been the objective of thorough studies, which link cardiovascular risk factors, vascular lesions and OAB. New animal models are being created to test new areas of treatment or prevention of ischemic-induced bladder dysfunction. Conclusion: Recent data point out that several physiological and pathological modifications that occur in the bladder associated with OAB and aging are closely related to ischemia.

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A Novel Mouse Model of Chronic Inflammatory and Overactive Bladder by a Single Intravesical Injection of Hydrogen Peroxide

Cited by 31 publications

References 57 publications

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction

Social stress induces changes in urinary bladder function, bladder NGF content, and generalized bladder inflammation in mice

Lower Urinary Tract Symptoms and Aging: The Impact of Chronic Bladder Ischemia on Overactive Bladder Syndrome

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