Scientists set new brain target for anti – nausea drugs science

Whether we got the flu or drank too much, most of us felt nauseous. However, unlike other universal sensations such as hunger and thirst, scientists still do not understand the biology behind feeling – or how to stop it. A new study in mice has identified a possible key player: specialized brain cells that communicate with the gut to rule out nausea.

This is an “elegant” study, says Nancy Thornbury, CEO of Kallyope, a biotechnology company focused on gut-brain interactions. Further research is needed to translate the finding into anti-nausea therapies, said Thornbury, who was not involved, but the data suggest possible leads to designing new interventions.

To conduct the study, Chuchu Zhang, a neuroscience postdoc at Harvard University, and her colleagues focused on the “area postrema,” a small structure in the brainstem first associated with nausea in the 1950s. Electrical stimulation of the region causes vomiting in animals.

Last year, Zhang’s team identifies two types of specialized excitatory neurons in the postrema area which induce nausea behavior in mice. Rodents cannot vomit, but shrink from discomfort when they feel sick. Zhang and her colleagues showed that excitatory neurons in the postrema region are responsible for this behavior by stimulating cells.

Genetic sequencing of cells in the postrema area also revealed inhibitory neurons in the region that scientists suspected could suppress the activity of excitatory neurons and play a role in stopping nausea. So in the new study, Zhang’s team injected mice with insulin insulinotropic peptide (GIP), a hormone extracted from the gut that humans and other animals produce after ingesting sugar and fat. Previous research on ferrets has shown that GIP inhibits vomiting, and Zhang suggests that it can suppress nausea to prevent us from losing valuable nutrients. She also believes it may play a role in activating neurons that inhibit nausea.

To test this hypothesis, the researchers gave the mice water-scented water filled with a nauseating substance. The animals began to avoid the scented water after a drink. But if the water also contained GIP, the rodents were happy to drink it again. When the team breeds mice that lack inhibitory neurons in the area of ​​the stoma, the addition of GIP to the water with toxins does not make a difference: the animals continue to avoid it in the future.

The findings suggest that GIP activates newly identified inhibitory neurons, which in turn block excitatory neurons in the postrema and suppress the feeling of nauseaThe team is graduating this month at Cell reports. Although the study focuses on the role that GIP secreted by the gut plays in suppressing nausea, Zhang adds that there may be additional factors in the body that can also activate inhibitory neurons to produce the same effect.

Another future area of ​​research is to clarify how the gut communicates with neurons in the postrema area. Zhang and her colleagues found that excitatory and inhibitory neurons in this region are connected to the gut via the vagus nerve, but how these brain cells actually “listen to the gut” and in turn send instructions to the gut is still unclear, Zhang said.

If the team’s explanation for the inhibitory and excitatory nerves in the postural area is correct, future pharmaceuticals modeled after GIP may be effective anti-nausea drugs, Thornbury said. Existing anti-nausea drugs mainly interfere with two main types of chemical receptors in brain cells, but scientists do not understand why they work. And in some conditions, such as nausea caused by chemotherapy and morning sickness, these drugs perform poorly, if at all.

The new drugs would be especially helpful for cancer patients, who often cite nausea as the main reason they can’t stick to treatment regimens, added Stephen Liberles, a senior researcher and molecular neurologist at Harvard.

Randy Seeley, an internist who studies gastrointestinal peptides at the University of Michigan, Ann Arbor, called the study a “good job.” The fact that the authors have combined multiple approaches to show that neurons in the postrema area are responsible for nausea, he says, “increases the confidence that the conclusions are correct.”

Still, Charles Horn, a neurologist who studies the communication between nerve organs and the side effects of cancer therapies at the University of Pittsburgh, would like to see additional experiments with ferrets that can vomit and have been used to test anti-nausea drugs.

Zhang acknowledges that more research is needed before scientists can fully understand nausea and how to treat it. For example, “We know that sometimes we can mentally suppress nausea,” she says. “So it may be that neurons are also receiving data from higher brain regions.

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