Dataset Information

Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense.

ABSTRACT: When bacteria enter the bladder lumen, a first-stage active defensive mechanism flushes them out. Although urinary frequency induced by bacterial cystitis is a well-known defensive response against bacteria, the underlying mechanism remains unclear. In this study, using a mouse model of acute bacterial cystitis, we demonstrate that the bladder urothelium senses luminal extracellular bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 and releases the transmitter ATP. Moreover, analysis of purinergic P2X₂ and P2X₃ receptor-deficient mice indicated that ATP signaling plays a pivotal role in the LPS-induced activation of L6-S1 spinal neurons through the bladder afferent pathway, resulting in rapid onset of the enhanced micturition reflex. Thus, we revealed a novel defensive mechanism against bacterial infection via an epithelial-neural interaction that induces urinary frequency prior to bacterial clearance by neutrophils of the innate immune system. Our results indicate an important defense role for the bladder urothelium as a chemical-neural transducer, converting bacterial LPS information into neural signaling via an ATP-mediated pathway, with bladder urothelial cells acting as sensory receptor cells.

SUBMITTER: Ueda N

PROVIDER: S-EPMC7713076 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense.

Ueda Norichika N Kondo Makoto M Takezawa Kentaro K Kiuchi Hiroshi H Sekii Yosuke Y Inagaki Yusuke Y Soda Tetsuji T Fukuhara Shinichiro S Fujita Kazutoshi K Uemura Motohide M Imamura Ryoichi R Miyagawa Yasushi Y Nonomura Norio N Shimada Shoichi S

Scientific reports 20201203 1

When bacteria enter the bladder lumen, a first-stage active defensive mechanism flushes them out. Although urinary frequency induced by bacterial cystitis is a well-known defensive response against bacteria, the underlying mechanism remains unclear. In this study, using a mouse model of acute bacterial cystitis, we demonstrate that the bladder urothelium senses luminal extracellular bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 and releases the transmitter ATP. Moreover, analys ...[more]

PMID: 33273625

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Project description:Recently, we found that gentle mechanical skin stimulation inhibits the micturition reflex in anesthetized rats. However, the central mechanisms underlying this inhibition have not been determined. This study aimed to clarify the central neural mechanisms underlying this inhibitory effect. In urethane-anesthetized rats, cutaneous stimuli were applied for 1 min to the skin of the perineum using an elastic polymer roller with a smooth, soft surface. Inhibition of rhythmic micturition contractions by perineal stimulation was abolished by naloxone, an antagonist of opioidergic receptors, administered into the intrathecal space of the lumbosacral spinal cord at doses of 2-20 μg but was not affected by the same doses of naloxone administered into the subarachnoid space of the cisterna magna. Next, we examined whether perineal rolling stimulation inhibited the descending and ascending limbs of the micturition reflex. Perineal rolling stimulation inhibited bladder contractions induced by electrical stimulation of the pontine micturition center (PMC) or the descending tract of the micturition reflex pathway. It also inhibited the bladder distension-induced increase in the blood flow of the dorsal cord at L5-S1, reflecting the neural activity of this area, as well as pelvic afferent-evoked field potentials in the dorsal commissure at the lumbosacral level; these areas contain long ascending neurons to the PMC. Neuronal activities in this center were also inhibited by the rolling stimulation. These results suggest that the perineal rolling stimulation activates the spinal opioidergic system and inhibits both ascending and descending transmissions of the micturition reflex pathway in the spinal cord. These inhibitions would lead to the shutting down of positive feedback between the bladder and the PMC, resulting in inhibition of the micturition reflex. Based on the central neural mechanisms we show here, gentle perineal stimulation may be applicable to several different types of overactive bladder.

Dataset Information

Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense.

Publications

Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense.

Similar Datasets

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