G protein-coupled receptor 55 activated by palmitoylethanolamide is associated with the development of nocturia associated with circadian rhythm disorders.

Aims: Bladder function is regulated by clock genes and dysregulation of circadian bladder function can cause nocturia. The blood concentration of palmitoylethanolamide (PEA), a fatty acid metabolite, changes with circadian rhythm. Clock gene abnormalities demonstrate the highest PEA levels during the sleep phase.

Potential Targets for Overactive Bladder in Older Men Based on Urinary Analysis of Metabolomics.

Objective: We investigated the association between overactive bladder (OAB) and urinary metabolites in men.

Methods: This prospective observational study included 42 men aged 65-80 years. The 3-day frequency volume chart (FVC), International Prostate Symptom Score (IPSS), and quality of life score were adapted to assess the micturition behavior.

Different effects of GsMTx4 on nocturia associated with the circadian clock and Piezo1 expression in mice.

Objectives: Nocturia is a major problem in geriatric patients. Clock genes regulate circadian bladder function and Piezo type mechanosensitive ion channel component 1 (Piezo1) that senses bladder fullness. We utilized WT and Clock mutant (Clock: nocturia phenotype) mice to determine if the effects of GsMTx4, a Piezo1 inhibitor, is dependent on circadian Piezo1 expression in the bladder.

Urinary metabolites identified using metabolomic analysis as potential biomarkers of nocturia in elderly men.

Purpose: To investigate the association between nocturia and urinary metabolites in elderly men using metabolomic analysis.

Methods: We recruited 66 men aged 65-80 years. The 3-day frequency volume chart (FCV), International Prostate Symptom Score (IPSS), and quality of life score were used to assess micturition behavior.

Author Correction: Intermittent restraint stress induces circadian misalignment in the mouse bladder, leading to nocturia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Metabolism of fatty acids and bile acids in plasma is associated with overactive bladder in males: potential biomarkers and targets for novel treatments in a metabolomics analysis.

Objectives: The present study was conducted to identify metabolites using a metabolomics approach and investigate the relationship between these metabolites and urgency as a major symptom of overactive bladder (OAB).

Patients And Methods: In 47 male participants without any apparent neurological disease, OAB was defined as an urgency score on the International Prostate Symptom Score of 2 and higher (OAB group, n = 26), while patients with a score of 1 or 0 were placed in a control group (n = 21). A comprehensive study on plasma metabolites was conducted, and metabolites were compared between the OAB and control groups.

Intermittent restraint stress induces circadian misalignment in the mouse bladder, leading to nocturia.

Intermittent stress disrupts the circadian rhythm in clock genes such as Per2 only in peripheral organs without any effect on the central circadian clock in the suprachiasmatic nucleus. Here, the effect of restraint stress (RS) on circadian bladder function was investigated based on urination behavior and gene expression rhythms. Furthermore, PF670462 (PF), a Per2 phosphorylation enzyme inhibitor, was administered to investigate the effects on circadian bladder re-alignment after RS.

The time-dependent variation of ATP release in mouse primary-cultured urothelial cells is regulated by the clock gene.

Aims: The sensation of bladder fullness (SBF) is triggered by the release of ATP. Therefore, the aim of this study was to investigate whether time-dependent changes in the levels of stretch-released ATP in mouse primary-cultured urothelial cells (MPCUCs) is regulated by circadian rhythm via clock genes.

Methods: MPCUCs were derived from wild-type and Clock mutant mice (Clock ), presenting a nocturia phenotype.

Metabolomic Analysis of Overactive Bladder in Male Patients: Identification of Potential Metabolite Biomarkers.

Objectives: To identify metabolites that are associated with an overactive bladder (OAB) using metabolomics.

Materials And Methods: A total of 58 male patients without apparent neurologic disease completed 24-hour bladder diaries of their micturition behavior and International Prostate Symptom Score (IPSS) for the assessment of micturition behavior and lower urinary tract symptoms. Urgency was defined as an IPSS urgency score of ≥2 (OAB group), and patients with IPSS urgency scores of ≤1 belonged to the control group.

The oscillation of intracellular Ca influx associated with the circadian expression of Piezo1 and TRPV4 in the bladder urothelium.

We previously showed that bladder functions are controlled by clock genes with circadian rhythm. The sensation of bladder fullness (SBF) is sensed by mechano-sensor such as Piezo1 and TRPV4 in the mouse bladder urothelium. However, functional circadian rhythms of such mechano-sensors remain unknown.

Development of novel and non-invasive diagnostic markers for lower urinary tract symptoms using urothelial cells in voided urine.

Objectives: We evaluated the association between lower urinary tract symptoms (LUTS) and the expression of connexin (Cx) and transient receptor potential (TRP) channel on urothelial cells non-invasively collected from voided urine in humans.

Methods: A total of 55 patients (36 males and 19 females, median age: 71 years old), who were followed up at University of Yamanashi Hospital, were enrolled in the present study. Urothelial cells were collected from voided urine of patients, and the mRNA expression of each subtype of Cxs and TRP channels was measured using quantitive real-time reverse transcription polymerase chain reaction.

The Circadian expression of Piezo1, TRPV4, Connexin26, and VNUT, associated with the expression levels of the clock genes in mouse primary cultured urothelial cells.

Aims: To investigate circadian gene expressions in the mouse bladder urothelium to establish an experimental model and study the functions of the circadian rhythm.

Methods: The gene expression rhythms of the clock genes, mechano-sensors such as Piezo1 and TRPV4, ATP release mediated molecules (ARMM) such as Cx26 and VNUT were investigated in mouse primary cultured urothelial cells (UCs) of wild-type (WT) and Clock mutant (Clock ) mice using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting analysis. The long-term oscillation of the clock genes in UC was investigated by measuring bioluminescence from UC isolated from Period2 knock-in mice (Per2::luc) and Per2::luc with Clock using a luminometer.

P2Y-deficiency increases micturition frequency and attenuates sustained contractility of the urinary bladder in mice.

The role of the P2Y receptor in bladder function has recently attracted a great deal of attention in lower urinary tract research. We conducted this study to determine contributions of the P2Y receptor in lower urinary tract function of normal phenotypes by comparing P2Y-deficient mice and wild-type mice. In in vivo experiments, P2Y-deficient mice had more frequent micturition with smaller bladder capacity compared to wild-type mice; however, there was no difference between these groups in bladder-filling pressure/volume relationships during cystometry under decerebrate, unanaesthetized conditions.