Inflammation of the airways can occur as a result of smoking or exposure to polluted air.
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Severe airway inflammation impairs mice's ability to learn when a dangerous situation is no longer a threat, suggesting that the lungs influence emotions and behavior. This connection between the lungs and the brain may also help explain why only a portion of people who experience trauma develop post-traumatic stress disorder (PTSD).
“Many of us see trauma, but only about 5 to 10 percent of people exposed to trauma actually suffer from PTSD,” says Renu Sah at the University of Cincinnati in Ohio. Previous research suggests that inflammation, especially in the lungs, may play a role. For example, among combat veterans. People with PTSD are about eight times more likely to have asthma.
Sah and her colleagues further examined this connection in eight mice with severe asthma-like symptoms. They exposed the animals' lungs to house dust mites, which caused an allergic reaction and inflammation. Three days later, they placed the mice in a cage and gave them three mild electric shocks.
For the next six days, the researchers returned the mice to their cage for 5 minutes each day, recording how long they stood frozen in fear. On average, they spent about 40 percent of their last session frozen—twice as much time as a separate group of 11 mice that didn't have pneumonia and were also given the shock.
There was no difference in freezing between the two groups the day after the shock, indicating that both had developed a fear response. However, the fact that the first group of mice became much more fearful after a few days suggests that severe airway inflammation is preventing brainthe ability to recognize when a previous threat has passed. “In patients with post-traumatic stress disorder, this process does not function properly, so they retain the memory of fear,” says Sah.
The researchers repeated this experiment in a separate group of mice with severe pneumonia, but this time they were given a drug that blocks the activity of an inflammatory molecule called interleukin-17A. During their final session in a cage where they had previously received electric shocks, these animals spent about half as much time frozen in fear as those that had not received the drug.
Further tests showed that immune cells in an area of the brain known as the subfornical organ have receptors for this molecule. Unlike most of the brain, the subfornical organ lacks the blood-brain barrier, a tightly sealed layer of cells that prevents most substances in the blood from reaching neurons. In this way, it acts as a “window into the brain,” allowing it to monitor what's going on in the body and respond accordingly, says Sah.
She and her colleagues found that immune cells in this area detect inflammatory molecules from the lungs, which activate nearby neurons. They then send a signal to the infralimbic cortex, an area of the brain involved in recognizing past threats.
The researchers suppressed this pathway in mice with severe pneumonia using special drugs, a technique called chemogenetics, which significantly reduced the time they froze in fear several days after the shock.
“So in a nutshell, pneumonia, especially severe pneumonia, can affect higher cortical function and your ability to process traumatic experiences,” says Sah. A similar pathway likely exists in humans, she said, because the brain circuitry that controls fear is similar in the two species.
Other studies have shown that Chronic psychological stress weakens immune responses. Sah suspects the opposite is happening here: the heightened immune response impairs psychological functions such as recognizing a past threat. This may be due to the body redirecting its resources away from the brain to deal with the threat in the lungs, she says.
“This research is important for better understanding how the body and mind are connected,” says Douglas Vanderbilt at Children's Hospital Los Angeles. This might also explain why his own research found that Children with severe asthma have more severe PTSD symptoms. “But I think we're learning that the brain-body interaction is very complex, so it's probably not the only way.” For example, the psychological stress of asthma attacks may also influence the risk of post-traumatic stress disorder, he says.
The study used only male mice, so the pathways may also differ in females, Sah says, and therefore may also differ in men and women, which requires further study.
However, these findings may help us better identify people who are more vulnerable to PTSD. For example, doctors may want to evaluate children with severe asthma for psychiatric disorders. health condition, Vanderbilt says. It could also lead to new treatments for PTSD, such as immune therapies that reduce inflammation, he said.
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