January 31, 2023

Credit: Emily Faith Morgan, University of Virginia Communications

The average person swallows 500 to 700 times a day. Imagine each of those swallows being a battle.

For many who suffer from esophageal motility disorders such as dysphagia, which affect the way the muscles in the esophagus deliver food and fluids to the stomach, swallowing can be difficult or even painful. It can turn something as simple as a sip of water into a violent coughing fit.

Caused by conditions such as gastroesophageal reflux disease (or GERD), degenerative diseases such as Parkinson’s disease and even just old age, these conditions can lead to problems such as dehydration, malnutrition, pneumonia and suffocation, and it affects the quality of life of approximately the half a million Americans a year and as many as one in five people over the age of 50.

The causes of these conditions are not well understood by medical science, but a study published this month in the journal Mobile Reports by a team of scientists from the University of Virginia’s College and Graduate School of Arts & Sciences and UVA’s School of Medicine identifies the unique genetic fingerprint of the nerve cells that control motor function of the esophagus. According to the scientists involved, this opens up a new approach to treating esophageal motility disorders that could lead to new therapies and new drugs, offering hope to those living with the debilitating effects of dysphagia and other conditions that affect the esophagus.

The study, led by doctoral student Tatiana Coverdell, began as an attempt to identify the brain’s neural pathways that control heart rate. The human body contains a complex set of neural pathways that connect the brain to each of the body’s organs, and much about how these pathways are organized and function is still not understood.

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Coverdell and her co-authors — John Campbell, a molecular neuroscientist and biology professor at the university, and Stephen Abbott, a pharmacology professor at the UVA’s School of Medicine — focused on an area of ​​the hindbrain in the lower part of the brainstem called the ambiguous core. Previous studies have suggested that the nucleus ambiguus is connected by nerve processes to the heart, larynx, pharynx (which carries air, food, and fluid down from the nose and mouth), and the esophagus, thus determining how they function. While looking for a specific route to the heart, they discovered a particular neuron subtype that powers axons (or nerve fibers) leading to the esophagus, which, when activated, causes esophageal contractions.

“Many of our projects start by generating a parts list for a particular part of the brain,” Campbell said. “We want to know all the different cells that make up that region and what they do, and we profile their gene expression to identify them. To find that out, we look at where each cell type sends their axons, because that tells us which organ.” it controls. That’s how we ended up on this road.”

Current therapies for esophageal disease include stimulation of the vagal nerves, the main nervous system that controls bodily functions called “resting and digesting,” which cannot be consciously controlled. However, that pathway also controls a host of other functions, such as cardio-respiratory and digestive functions, and these therapies can cause a variety of unwanted effects.

“The vagus nerve is a superhighway of information between all of your visceral organs and your brain, and these motor neuron axons are found in it,” Campbell said. “But when you stimulate that, you activate everything: all these different pathways between the brain and the other connected organs. With a more focused approach to only affect motor function of the esophagus, these therapies could be more accurate.”

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Realizing that their findings could have practical clinical applications, Campbell and Coverdell reached out to neurophysiologist Stephen Abbott to help them characterize the function of the cells they discovered.

“The discovery has a lot of clinical significance because it allows us to target the esophagus more specifically rather than the whole region and with many off-target effects,” Coverdell said. “Future research may look at this and develop more targeted therapies for swallowing disorders.”

“We now have a complete gene expression profile for these esophageal motor neurons,” Campbell added. “We know all the receptors they express, all the neuropeptides and other signals they express — any of these could be pharmacological targets in the treatment of esophageal motility disorder. It also gives us access to the entire neural circuitry that controls swallowing.” So we can work backwards from these neurons that control the contractions of the esophagus, and that will give us a complete picture of how the swallowing program is displayed in the brain.”

Abbott agrees that the discovery will have significant implications for medicine, especially as the US population continues to age.

“The ability to identify and study the nerve cells that control esophageal function allows us to study problems with esophageal motility disorders, and we hope this will advance improved treatments for these conditions that are common in the elderly,” Abbott said. “We have all the options in front of us now that we have this information.”

According to Deborah Roach, chair of the College’s Department of Biology, the findings are important evidence of the role interdisciplinary research plays in pushing the boundaries of both science and medicine.

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“This is a wonderful example of how collaboration between basic research done in the Department of Biology at the College of Arts & Sciences and applied research done in the School of Medicine can potentially lead to major breakthroughs,” she said.

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More information:
Tatiana C. Coverdell et al, Genetic encoding of an esophageal motor circuit, Mobile Reports (2022). DOI: 10.116/j.celrep.2022.110962

Provided by the University of Virginia

Quote: Study Could Lead to New Treatments for Swallowing Disorders (2022, Aug 8), retrieved Aug 8, 2022 from https://phys.org/news/2022-08-treatments-swallowing-disorders.html

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