Adult man in a toilet at home

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BETHESDA, Md. — Everyone knows that urge “to go” when they feel it. So how does your brain even know when it’s time to run to the bathroom? A study has uncovered one gene that may be the key to the urge to urinate. Researchers add that when this gene isn’t working properly it can mean big trouble for your health.

“Urination is essential for our health. It’s one of the primary ways our bodies dispose of waste. We show how specific genes and cells may play critical roles in initiating this process,” says senior author Ardem Patapoutian of the Scripps Research Institute in a media release. “We hope that these results provide a more detailed understanding of how urination works under healthy and disease conditions.”

The study finds the gene PIEZO2 is likely responsible for the human urge to urinate. This gene acts on at least two different types of cells which senses when our bladders are full and need to be emptied. Urine is created when the kidneys move waste and excess water from the blood stream. These substances are sent to the bladder, filling it up like a water balloon. Bladder muscles tense up as the bladder fills, eventually sending out this signal that it’s time to go.

The connection between PIEZO2 and the urge to urinate

Researchers in the National Institutes of Health (NIH)-funded study say PIEZO2 contains instructions for creating proteins which go to work when cells are stretched or squeezed. In this study, the team looked at what happens when the body does not have enough PIEZO2.

Tests on mice reveal those who are deficient in PIEZO2 have issues sensing when their bladders are full. This connection suggested to the scientists that bladder cells understand when the organ is filling and this sparks neurons which relay this tension to the body’s nervous system.

“There were a lot of reasons to think that PIEZO2 could be important for urination. Theoretically, it made sense as it is a pressure sensor for other internal sensory processes,” explains Kara L. Marshall, a post-doctoral fellow on Dr. Patapoutian’s team.

10 years of gene research

Researchers first discovered PIEZO2, along with a similar gene called PIEZO1, in mouse brain tumors back in 2010. Studies on the gene in flies, worms, and mice revealed it plays several roles throughout the body in terms of sensing pain, vibrations, touch, and spatial orientation.

In 2015, NIH scientists had a breakthrough in PIEZO2 research. They discovered people born with a mutation which disables this gene could not feel some forms of pain or touch. These patients also had another thing in common: urinary issues.

“We were really struck by what we heard during background interviews with patients and their families. Almost everyone mentioned that the patients had problems with urination. As children, they had trouble potty training. They would often have urinary tract infections. And most of them follow a daily urination schedule,” researcher Dimah Saade reports. “After seeing a consistent pattern, we decided to take a closer look.”

Examining medical records, ultrasound scans, and questionnaires of 12 patients and their families uncovered that PIEZO2-deficient people can go an entire day and only urinate once or twice. On average, the normal human will urinate five or six times a day.

The examinations found that these patients were also dealing with trouble urinating and needed to press on their stomachs to go. Five of the 12 said the urge to go only comes on suddenly at the last moment.

“These results strongly suggested that PIEZO2 plays a role in urination,” Dr. Marshall adds. “We wanted to know how it may do this.”

Mice without PIEZO2 battle incontinence

The new study on mice finds the PIEZO2 gene is highly active in the dorsal root ganglion (DRG) neurons. These brain cells send nerve signals from the animal’s bladder to their brains. The gene also activates some “umbrella” cells which line the inside of a bladder.

“These were the first clues to understanding where in the urinary tract PIEZO2 worked. They suggested that it may help control the bladder,” says study co-author Nima Ghitani.

When the researchers deleted this gene from mice they discovered more evidence PIEZO2 is the key to the urinating urge. Mice without the gene showed signs of incontinence and began to urinate in random areas of their cages. These mice also developed thicker bladder muscles, suggesting that losing the sense to urinate also changes how our bodies grow.

“Neurologists have always known that there’s a strong link between the nervous system and bladder control, both on a conscious as well as on an automatic level,” senior investigator Dr. Carsten Bönnemann explains. “Our patients together with the results in the mouse models teach us how the loss of the critical sensor PIEZO2 profoundly disrupts the wiring behind normal bladder control, ultimately reshaping the bladder itself.”

The study appears in the journal Nature.

About Chris Melore

Chris Melore has been a writer, researcher, editor, and producer in the New York-area since 2006. He won a local Emmy award for his work in sports television in 2011.

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