Gut neurons may offer way to treat constipation in Parkinson’s: Study
Discovery in mice may have implications for patients with digestive issues
Neurons, or nerve cells, that release a signaling molecule called glutamate within the enteric nervous system — a network of nerve cells embedded in the gut wall — play a crucial role in regulating bowel movements, according to a Stanford University study that ultimately could lead to new ways to treat constipation in Parkinson’s disease.
The researchers noted that this discovery in mice may have implications for Parkinson’s patients, who often experience constipation and other digestive issues.
“Our results posit glutamatergic neurons as key interneurons [connecting neurons] that regulate intestinal motility,” or the coordinated muscle movements in the gastrointestinal tract that process food and waste through the digestive system, the researchers noted.
“Future work should further explore the active roles that [these] interneurons play in processing information in the [enteric nervous system],” the team wrote.
Julia Kaltschmidt, PhD, who led the study, is focused on quantifying the gut’s ability to move matter through it.
“[The enteric nervous] system not only keeps the gut working, but plays a central role in health and disease and perhaps even in our experience of the mind,” Kaltschmidt, an associate professor of neurosurgery at Stanford University School of Medicine, said in a Stanford news story.
The study, “Enteric glutamatergic interneurons regulate intestinal motility,” was published in the journal Neuron.
Study of constipation, digestive issues focuses on gut’s nervous system
In Parkinson’s disease, protein clumps, or aggregates, known as Lewy bodies are believed to first form in the gut lining before traveling along the vagus nerve — the body’s longest nerve — to the brain. There, they become toxic to dopaminergic neurons, the nerve cells responsible for producing dopamine, a key chemical that regulates movement.
While the disease is best known for its motor symptoms, people with Parkinson’s also experience nonmotor symptoms like constipation and other digestive problems, including slow digestion and heartburn. Some of these nonmotor symptoms often appear years before motor symptoms manifest.
In this study, Kaltschmidt’s team sought to better understand how the enteric nervous system controls the digestive system. To learn more, the scientists focused on nerve cells in the gut that release a neurotransmitter called glutamate, which plays a key role in regulating the contraction and relaxation of intestinal muscles, helping to move food through the digestive tract.
In the mouse gut, the researchers identified two types of neurons expressing vesicular glutamate transporter 2, called VGLUT2, which is a protein that regulates glutamate storage and release. One type extended along the length of the small intestine and the colon, while the other formed circular networks within the colon.
Both types were interneurons, or neurons that connect other nerve cells to facilitate communication and information processing. In the gut, digestion begins when sensory nerves, which detect food, relay signals to motor nerves, responsible for movement, through interneurons.
These neurons were shown to use glutamate as well as other neurotransmitters, such as acetylcholine and enkephalin, to regulate gut muscle movement and propel food through the digestive tract. The team noted that “future experiments should aim to disentangle the effects of glutamate from co-released molecules.”
Eating and digesting is really at the core of being a freely moving and thinking organism, and we’re increasingly recognizing the importance of the enteric nervous system in this more general sense.
When researchers removed VGLUT2 from some of these neurons, the mice passed food faster — in about half the time — through their gut and produced more but smaller fecal pellets than wild-type (normal) mice. Stimulating these neurons in a lab setting could make the colon move food forward, suggesting they’re key to control bowel movements, according to the scientists.
Kaltschmidt’s team is now aiming to develop what’s essentially a gut pacemaker to regulate bowel movements. This potentially could help treat chronic constipation — which can occur not only with diseases like Parkinson’s but in normal aging.
“Eating and digesting is really at the core of being a freely moving and thinking organism, and we’re increasingly recognizing the importance of the enteric nervous system in this more general sense,” Kaltschmidt said.
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