summary: A small group of airway neurons plays a key role in altering the brain in the presence of influenza infection in the body, and a second pathway from the lung to the brain is activated late in infection. The results also shed light on how NSAID anti-inflammatory drugs can alleviate flu symptoms.
sauce: harvard
A new study led by researchers at Harvard Medical School reveals how the brain recognizes that there is an infection in the body.
A team that studied mice found that a small group of neurons in the airways played a pivotal role in alerting the brain to flu infections. They also found signs that a second pathway from the lungs to the brain is activated later in the infection.
This research Nature.
Most people get sick several times a year, but scientific knowledge of how the brain evokes feelings of sickness lags behind research on other physical conditions such as hunger and thirst. This paper represents an important first step towards understanding the brain-body connection during infection.
“This study will help us begin to understand the underlying mechanisms of pathogen detection and how it relates to the nervous system, which has been largely a mystery until now,” says Bravatnik of HMS. said senior author Stephen Liberles, a professor of cell biology at the Institute. A researcher at the Howard Hughes Medical Institute.
The findings also shed light on how non-steroidal anti-inflammatory drugs such as ibuprofen and aspirin relieve flu symptoms.
If this result can be applied to humans, it may have important implications for developing more effective influenza treatments.
contagious mental state
The Liberles lab is interested in how the brain and body communicate to control physiology. For example, we have previously investigated how the brain processes sensory information from internal organs and how sensory cues can trigger or suppress the sensation of nausea.
In a new paper, researchers turn their attention to another important type of disease controlled by the brain: diseases caused by respiratory infections.
During an infection, the brain coordinates symptoms as the body mounts an immune response, said Liberles. These include a wide range of symptoms such as fever, loss of appetite and lethargy, as well as specific symptoms such as congestion and coughing due to respiratory illness and vomiting and diarrhea due to gastrointestinal illness.
The team decided to focus on influenza, a respiratory virus that causes millions of illnesses and hospital visits in the United States each year, and thousands of deaths.
Through a series of mouse experiments, lead author Na-Ryum Bin, an HMS researcher at the Liberless Institute, identified a small population of neurons embedded in the glossopharyngeal nerve, which runs from the throat to the brain.
Importantly, he found that these neurons were necessary to signal to the brain that an influenza infection was present and had receptors for lipids called prostaglandins. , are made in both mice and humans during infection and are targeted by drugs such as ibuprofen and aspirin.
Cutting the glossopharyngeal nerve, removing neurons, blocking prostaglandin receptors in those neurons, or treating mice with ibuprofen similarly reduced influenza symptoms and increased survival.
These results suggest that these airway neurons detect prostaglandins made during influenza infection and become a pathway for transmission from the upper throat to the brain.
“We think these neurons relay information that pathogens are there and initiate neural circuits that control disease responses,” said Liberles.
The results explain how drugs such as ibuprofen and aspirin reduce flu symptoms and suggest that these drugs may even improve survival.
Researchers have found evidence of another potential disease pathway. This is the pathway that travels from the lungs to the brain. They found that the virus appears to activate during a second stage of infection as it penetrates deeper into the respiratory system.
The team was surprised to find that this additional pathway did not involve prostaglandins. Mice in the second stage of infection did not respond to ibuprofen.
The findings suggest an opportunity to improve flu treatment if scientists can develop drugs that target additional pathways, the authors said.
Foundation for future research
The study raises many questions that Liberless and colleagues are eager to explore.
One is how well the findings translate to humans. Mice and humans share much of the basic sensory biology, including the glossopharyngeal nerve, but researchers believe humans have the same neuronal populations and pathways seen in mouse studies. He emphasized that researchers need to do more genetic and other experiments to confirm.
If the findings can be replicated in humans, it increases the likelihood of developing therapeutics that address both prostaglandin and non-prostaglandin pathways of influenza infection.
“If we can find a way to inhibit both pathways and use them synergistically, that could be very exciting and potentially transformative.
See also
Bing has already delved into the details of the non-prostaglandin pathway involving the neurons involved, with the goal of figuring out how to block it. We want to identify cells and study them in greater depth.
Liberles is excited to explore the full diversity of disease pathways in the body to see if they specialize in different types and sites of infection. Things could help scientists learn how to manipulate them to better treat various ailments, he said.
About this neuroscience research news
author: press office
sauce: harvard
contact: Press Office – Harvard
image: image is public domain
Original research: open access.
“Airway-to-brain sensory pathways mediate influenza-induced diseaseBy Steven Liberless et al. Nature
overview
Airway-to-brain sensory pathways mediate influenza-induced disease
Pathogen infections cause stereotypical disease states with neuronal orchestrated behavioral and physiological changes.
Upon infection, immune cells release a ‘storm’ of cytokines and other mediators, many of which are detected by neurons. However, the responsive neural circuitry and neuroimmune interaction mechanisms that drive disease behavior during naturalistic infections remain unclear.
Over-the-counter drugs such as aspirin and ibuprofen are widely used to alleviate the disease and act by blocking prostaglandin E2 (PGE2) synthesis. The leading model is that PGE2 crosses the blood-brain barrier and directly engages hypothalamic neurons.
Here, using genetic tools broadly covering the Atlas of Peripheral Sensory Neurons, we instead identified a small population of PGE2-sensing glossopharyngeal sensory neurons (pyramidal GABRA1 neurons) that are essential for influenza-induced disease behavior in mice. .
Ablation of pyramidal GABRA1 neurons or targeted knockout of the PGE2 receptor 3 (EP3) in these neurons reversed the reduced food intake, water intake, and mobility during early infection with influenza and improved survival. improve. Genetically-guided anatomical mapping reveals that pyramidal GABRA1 neurons have increased expression of cyclooxygenase-2 after infection and project to mucosal regions of the nasopharynx, and also display specific axonal targeting patterns in the brainstem. became.
Together, these findings uncover key airway-to-brain sensory pathways that detect locally generated prostaglandins and mediate systemic disease responses to respiratory viral infections.
