Overview: After eating contaminated food, the toxin activates the release of serotonin by enterochromaffin cells lining the intestinal lumen. It signals along the nerve to neurons of the dorsal vagus nerve complex, inducing nausea behavior.
sauce: Celpress
The urge to vomit after eating contaminated food is the body’s natural defense response to rid itself of bacterial toxins. remains elusive.
For the first time, researchers have mapped the detailed neural pathways of defense responses from the gut to the brain in mice.
The study was published in the journal Nov. 1. cellcan help scientists develop better anti-nausea drugs for cancer patients undergoing chemotherapy.
Many food poisoning bacteria produce toxins within the host after ingestion. After the brain senses their presence, it initiates a series of biological responses, including vomiting and nausea, to get rid of the substances and develop an aversion to foods that taste or look the same.
“However, the details of how signals are transmitted from the gut to the brain were unknown because scientists were unable to study the process in mice,” said the paper at the National Institute of Biological Sciences in Beijing. Author Peng Cao says: Rodents cannot vomit, probably because they have a long esophagus and weak muscles relative to their size.
As a result, scientists have studied the vomit of other animals such as dogs and cats, but these animals have not been comprehensively studied and the mechanisms of nausea and vomiting have not been clarified. did.
Cao and his team found that mice do not vomit, but they do.
The team found that mice developed episodes of abnormal mouth opening after being administered staphylococcal enterotoxin A (SEA), a common bacterial toxin produced by Staphylococcus aureus that also leads to food poisoning in humans. did.
Mice that received SEA opened their mouths at a wider angle than that observed in the control group in which mice received saline. The abdominal muscles contract at the same time. This is the pattern you see when your dog is vomiting. During normal breathing, an animal’s diaphragm and abdominal muscles contract alternately.
“The neural mechanisms of nausea are similar to those of vomiting. In this experiment, we successfully constructed a paradigm for studying toxin-induced retching in mice, and found that the brain responds to toxins at the molecular and cellular levels.” We can look at the defensive responses of the animals,” says Cao.
The team found that in mice treated with SEA, intestinal toxins activated the release of serotonin, a type of neurotransmitter, by enterochromaffin cells lining the intestinal lumen.
The released serotonin binds to receptors on vagal sensory neurons in the gut and sends signals along the vagus nerve from the gut to specific types of neurons in the dorsal vagal complex (Tac1 + DVC neurons) in the brainstem. I will send.
When Cao and his team inactivated Tac1+DVC neurons, mice treated with SEA had less swelling compared with mice with normal Tac1+DVC neuron activity.
Additionally, the team investigated whether chemotherapeutic drugs that induce defensive responses such as nausea and vomiting in recipients activate the same neural pathways.
They injected mice with doxorubicin, a common chemotherapy drug. The drug caused nausea in the mice, but when the team inactivated serotonin synthesis in his Tac1+ DVC neurons or enterochromaffin cells in mice, the mice’s nausea behavior was greatly reduced.
Some of the current anti-nausea drugs for patients undergoing chemotherapy, such as granisetron, work by blocking serotonin receptors, Cao said. This study helps explain why the drug works.
“This study will allow us to better understand the molecular and cellular mechanisms of nausea and vomiting, which will help us develop better treatments,” said Cao.
Next, Cao and his colleagues would like to examine how the toxin acts on enterochromaffin cells. Preliminary studies have shown that enterochromaffin cells do not directly sense the presence of toxins. This process may involve a complex immune response of damaged cells in the gut.
“In addition to food-borne pathogens, humans encounter many pathogens, and our bodies have similar mechanisms to excrete these toxins.
“Coughing, for example, is our body’s attempt to get rid of coronaviruses. This is a new and exciting look at how the brain senses the presence of pathogens and initiates a response to get rid of them.” It’s an exciting area of research,” Cao said, adding that future research could reveal new and better targets for drugs, including anti-nausea medications.
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About this neuroscience research news
author: press office
sauce: Celpress
contact: Press Office – Cell Press
image: image is public domain
Original research: open access.
“Gut-to-brain axis of toxin-induced defense responses” by Peng Cao et al. cell
Overview
Gut-to-brain axis of toxin-induced defense responses
highlight
- Mice show nausea and nausea to bacterial toxins and chemotherapy drugs
- Identification of a molecularly defined gut-to-brain circuit for nausea and retching
- Distinct Brainstem Circuits Cause Nausea and Nausea
- Toxin-induced signals may be mediated through the immune-neuroendocrine system of the gut
Overview
After ingesting toxin-contaminated food, the brain initiates a series of protective responses (such as nausea, nausea, and vomiting). How the brain detects ingested toxins and coordinates various protective responses is still poorly understood.
Here, we have developed a mouse-based paradigm to study defense responses induced by bacterial toxins. Using this paradigm, we identified a set of molecularly defined gut-to-brain and brain circuits that collectively mediate toxin-induced defensive responses.
The circuit from the gut to the brain is Htr3a+ Vagus sensory neurons that transmit toxin-related signals from enterochromaffin cells Tac1+ Neurons of the dorsal vagus nerve complex (DVC).
Tac1+DVC neurons drive nausea-like behavior and conditioned taste avoidance via divergent projections to the rostral-ventral respiratory group and the lateral parabrachial nucleus, respectively. Manipulation of these circuits also interferes with the protective responses induced by the chemotherapy drug doxorubicin.
These results suggest that food poisoning and chemotherapy recruit similar circuit modules to initiate protective responses.
