Summary: The new study identified a specific group of neurons in the brainstem that controls the sickness behaviors in response to bacterial infection. These neurons sit in the nucleus of the solitary tract (NTS) and the area postrema (AP). When they switch on, they cause loss of appetite, less thirst, less physical activity, and changes in body temperature. The researchers also found that blocking these neurons reduced the sickness behaviors caused by the bacterial endotoxin (a toxin from the bacteria’s outer wall).
When we catch an infection, our immune system sets off a chain of responses to fight the invading germs. Sadly, these responses can cause symptoms that make us feel sick. These include loss of appetite, less thirst, and less physical activity. One way infections make us feel sick is by triggering the release of cytokines. Cytokines are signaling molecules that play a key role in our immune response. They cause inflammation and fever, and that makes us feel tired and sluggish. Cytokines can also signal the brain to cut appetite and lower our drive to eat. That leads to weight loss and malnutrition. In the same way, the body’s response to infection can also make us drink less water, which leads to dehydration. This may also have some protective role, though how it helps is not fully understood yet. Moving less during sickness is another hallmark of illness. It lets the body save energy and focus its resources on fighting the infection. Physical activity can also increase inflammation and make the symptoms of illness worse.
These symptoms may be unpleasant, but they play an important role in helping us recover from infections. For example, loss of appetite can help starve the germs, which stops them from growing and spreading. In the same way, moving less can save energy, so the body can focus on the immune response. Finally, dehydration can limit the growth of bacteria and viruses, which helps fight off the infection.
Which brain cells cause sickness behavior?
We have long known about sickness behavior and its role in fighting infections. What was missing was the brain wiring behind it. Until now, we did not know exactly how these changes in behavior happen. A new study published in the journal Nature has identified the exact underlying mechanism causing sickness behavior. The new study looked at the set of behaviors animals show when they are sick. These include loss of appetite, less thirst, less physical activity, and changes in body temperature. Together these are called “sickness behaviors” and they are adaptive. They help the body fight off infection. But it was not clear how the brain controlled them.
The study used several methods to find a specific group of neurons in the brainstem that controls the sickness behaviors. These neurons respond to a bacterial endotoxin called lipopolysaccharide (LPS). First, the researchers used whole-brain activity mapping to see which neurons switched on after LPS treatment. They found that a subset of neurons in the nucleus of the solitary tract (NTS) and the area postrema (AP) were activated. Next, the researchers used a genetic method to switch on only these neurons in mice. Doing so copied the sickness behaviors caused by LPS. They also found that blocking these neurons weakened the behavioral responses to LPS. Further testing with single-nucleus RNA sequencing pinned down a specific group of neurons that switched on in response to LPS and caused the sickness behaviors. These neurons sat in the NTS-AP and expressed a specific gene called ADCYAP1. The researchers concluded that the pleiotropic (many-sided) effects of LPS on sickness behaviors are controlled by a specific group of neurons in the NTS-AP. These neurons are necessary and sufficient for the sickness response. This sets up a key link between the brain and the body’s response to infection.
This finding matters because it helps explain how the body responds to infections and how the brain controls those responses. Knowing the brain wiring behind sickness behaviors may lead to new treatments for infections that target these specific neurons. This research may also help us understand the brain’s role in other body responses to disease and injury.
Frequently asked questions
Why do you feel so tired when you are sick?
An infection sets off your immune system, which releases signaling molecules called cytokines. Cytokines cause inflammation and fever, and that is what makes you feel tired and sluggish. Slowing down also has a purpose. Resting saves energy so the body can put its resources into fighting the infection. In animal studies, a specific group of brain stem neurons in the NTS and area postrema drives this slowdown.
Is it better to rest when you are sick?
Yes. Moving less during an illness lets the body save energy and focus on the immune response. Physical activity can also increase inflammation and make the symptoms of illness worse. The tiredness you feel is not a failure of willpower. It is part of an adaptive response that helps the body fight off the infection and recover.
What is sickness behavior?
Sickness behavior is the set of changes people and animals show when they are sick. These are loss of appetite, drinking less, moving less and changes in body temperature. These changes are adaptive, meaning they help the body fight off infection. A study in Nature traced them to one group of neurons in the brain stem. In mice, those neurons were both necessary and sufficient for the sickness response.
Why do you lose your appetite when you are sick?
Cytokines released during an infection signal the brain to turn down appetite and reduce the drive to eat. Eating less may help starve the invading germs and limit their growth and spread. In mice, switching on a group of brain stem neurons that express the ADCYAP1 gene copied this loss of appetite. Switching them off reduced it.
Dr. Gurpreet Singh Padda, MD, MBA, MHP
