A new study has identified, in mice, specific cells and proteins that control the sneeze reflex.
Better understanding of what causes us to sneeze, and especially how neurons behave in response to allergens and viruses, may lead to treatments which can slow the spread of infectious respiratory diseases.
A tickle in the nose can help trigger a sneeze, which expels irritants and disease-causing pathogens. But the cellular pathways that control the sneeze reflex go far beyond the sinuses and have been poorly understood. Now, a team led by researchers at Washington University School of Medicine in St. Louis has identified, in mice, specific cells and proteins that control the sneeze reflex.
“Better understanding what causes us to sneeze — specifically how neurons behave in response to allergens and viruses — may point to treatments capable of slowing the spread of infectious respiratory diseases via sneezes,” said Qin Liu, PhD, an associate professor of anesthesiology and the study’s senior investigator.
“We study the neural mechanism behind sneezing because so many people, including members of my own family, sneeze because of problems such as seasonal allergies and viral infections,” explained Prof Liu, a researcher in the university’s Center for the Study of Itch and Sensory Disorders. “Our goal is to understand how neurons behave in response to allergies and viral infections, including how they contribute to itchy eyes, sneezing and other symptoms. Our recent studies have uncovered links between nerve cells and other systems that could help in the development of treatments for sneezing and for fighting infectious respiratory diseases.”
Sneezing is the most common and forceful way of spreading infectious droplets from respiratory infections. Over two decades ago, researchers discovered a sneeze-evoking region in the central nervous system, but since then there has been little progress in understanding the mechanism of the sneeze reflex at the cellular and molecular level.
For the new study, Prof Liu and her team used a mouse model to figure out which nerve cells send signals that make mice sneeze. The researchers exposed the mice to aerosolised droplets containing either histamine or capsaicin, a pungent compound made from chili peppers, both of which caused the mice to sneeze.
By examining nerve cells that already were known to react to capsaicin, Liu’s team was able to identify a class of small neurons linked to sneezing that was caused by that substance. The researchers then searched for neuropeptides that could transmit sneeze signals to those nerve cells, and hit upon a molecule called neuromedin B (NMB), which they found was required for sneezing.
By eliminating the NMD-sensitive neurons in the part of the nervous system that evoked sneezes in the mice, they blocked the sneeze reflex. Those neurons all make a protein called the neuromedin B receptor. In mice lacking that receptor, sneezing again was greatly reduced.
“Interestingly, none of these sneeze-evoking neurons were housed in any of the known regions of the brainstem linked to breathing and respiration,” Prof Liu said. “Although we found that sneeze-evoking cells are in a different region of the brain than the region that controls breathing, we also found that the cells in those two regions were directly connected via their axons, the wiring of nerve cells.”
By exposing part of the mouse brain to the NMB peptide, the researchers found they could directly stimulate the sneeze reflex, even though they had not been exposed to any capsaicin, histamine or other allergens.
Since many viruses and other pathogens are spread in part by aerosolised droplets, Prof Liu said it may be possible to limit the spread of those pathogens by targeting NMB or its receptor to limit sneezing in those known to be infected.
“A sneeze can create 20 000 virus-containing droplets that can stay in the air for up to 10 minutes,” Liu Prof explained. “By contrast, a cough produces closer to 3000 droplets, or about the same number produced by talking for a few minutes. To prevent future viral outbreaks and help treat pathological sneezing caused by allergens, it will be important to understand the pathways that cause sneezing in order to block them. By identifying neurons that mediate the sneeze reflex, as well as neuropeptides that activate these neurons, we have discovered targets that could lead to treatments for pathological sneezing or strategies for limiting the spread of infections.”
Source: Washington University School of Medicine
Journal information: Li, F., et al. (2021) Sneezing reflex is mediated by a peptidergic pathway from nose to brainstem. Cell. doi.org/10.1016/j.cell.2021.05.017.
