Research can help develop better treatments for difficulty swallowing

Sensory cells in the vagus nerve can detect and locate food in the esophagus. Their signals help transport the food further to the stomach. Signal failure leads to swallowing disorders, says a team led by Carmen Birchmeier at the Max Delbrück Center. They have published their findings in “Neuron.”

Difficulty swallowing can have many causes, and they occur more frequently in older people. But neurological diseases such as multiple sclerosis and Parkinson’s disease and certain medications can also prevent food from moving normally from the mouth to the stomach. Possible consequences include malnutrition, weight loss and dehydration.

Now a team led by Professor Carmen Birchmeier, who runs the Developmental Biology/Signal Transduction Laboratory at the Max Delbrück Center in Berlin, has investigated the swallowing process in more detail. Writing in the journal”Neuron“, the researchers describe how sensory cells in the vagus nerve respond to mechanical stimuli in the esophagus and trigger involuntary muscle movement, a process known as esophageal peristalsis. The vagus nerve, one of the 12 cranial nerves, provides information about the status of internal nerves. organs to the brain. The team’s study results may ultimately lead to better treatments for swallowing difficulties.

Swallow on camera

“Modern methods of single-cell sequencing made our work possible,” explains Birchmeier. “Using the sequencing data, we constructed genetic models that allowed us to study the functions of the sensory neurons in the vagal ganglia in more detail.” Ganglia are a group or “node” of neuronal bodies in the peripheral nervous system.

The researchers began by staining the neurons to see which organs they innervate. They then determined whether and how they responded to mechanical stimuli in the esophagus. Finally, they disabled the cells to analyze how this affected swallowing. Dr. Teresa Lever of the University of Missouri School of Medicine in Columbia, USA, developed a method that allowed the researchers to use videofluoroscopy to observe swallowing in freely behaving, unanesthetized mice in real time.

More than just a pipe

“When mice lost the neurons that provide information about mechanical stimuli in the esophagus, they lost the ability to reflexively perform the appropriate muscle movements that transport food to the stomach, and they rapidly lost weight,” says lead author Dr. Elijah Lowenstein, who obtained his Ph.D. by working on this study in Birchmeier’s team. He is now a researcher at Harvard Medical School in Boston. The weight loss, says Lowenstein, shows that the neurons play a key role in bodily homeostasis.

“So the esophagus is not just a tube that connects the mouth to the stomach,” he says. “It uses mechanosensory feedback to fulfill its function.” Birchmeier adds that without these cells in the vagus nerve, food gets stuck in our esophagus. In some of the mice, it actually flowed back into the throat.

A molecular atlas for everyone

“Our work can now help develop better treatments for swallowing difficulties. One possibility would be to pharmacologically activate the mechanoreceptors we identified,” says Birchmeier. She also wants to use the genetic models to determine the functions of other vagal sensory neurons — such as those that control the lungs or the aorta.

“These neurons likely play a crucial but as yet unknown role in the development of certain respiratory diseases or cardiovascular diseases such as hypertension,” she says. Other researchers can also participate in these projects, as Birchmeier and her team have developed a molecular atlas of all vagal neurons in mice. The atlas is freely available online.


Max Delbrück Center for Molecular Medicine in the Helmholtz Association

Journal reference:

Elijah D. Lowenstein et al. (2023): “Prox2 and Runx3 vagal sensory neurons regulate esophageal motility.” Neuron, DOI: 10.1016/j.neuron.2023.04.025

Research can help develop better treatments for difficulty swallowing

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