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 are located in the nucleus of the solitary tract (NTS), and the area postrema (AP), and their activation leads to loss of appetite, reduced thirst, decreased physical activity, and changes in body temperature. The researchers also found that inhibiting these neurons reduced the sickness behaviors induced by the bacterial endotoxin.
When we contract an infection, our body’s immune system triggers a series of responses to fight off the invading pathogens. Unfortunately, these responses can cause a range of symptoms that make us feel sick, including loss of appetite, reduced thirst, and decreased physical activity.
One of the ways infections make us feel sick is by triggering the release of cytokines, which are signaling molecules that play a critical role in our immune response. These cytokines induce inflammation and cause fever, making us feel tired and lethargic. Additionally, cytokines can signal the brain to decrease appetite and reduce our motivation to eat, leading to weight loss and malnutrition.
Similarly, the body’s response to infections can also cause us to drink less water, leading to dehydration. This may also have some protective role, though how it helps is not fully understood yet.
Reduced physical activity during sickness is another vital sign of illness. It allows the body to conserve energy and focus its resources on fighting off the infection. Additionally, physical activity can increase inflammation and worsen the symptoms of illness.
Although these symptoms may be uncomfortable, they play an important role in helping us recover from infections. For example, loss of appetite can help starve the pathogens, preventing their growth and spread. Similarly, decreased physical activity can conserve energy, allowing the body to focus on the immune response. Finally, dehydration can limit the growth of bacteria and viruses, helping to fight off the infection.
Researchers identify the neuronal pathway responsible for inducing sickness behavior
Although we have long known about the sickness behavior and its role in fighting infections, what has been missing is our knowledge about underlying neural mechanisms. To date, we did not know how these behavioral changes occur exactly. A new study published in the journal Nature has identified the exact underlying mechanism causing sickness behavior.
The new study focused on the set of behaviors that animals display when they are sick, including loss of appetite, reduced thirst, decreased physical activity, and changes in body temperature. These behaviors are collectively called “sickness behaviors” and are adaptive responses to help the body fight off infection. However, it was not clear how these behaviors were controlled in the brain.
The study used various techniques to identify a specific group of neurons in the brainstem that controls the sickness behaviors in response to a bacterial endotoxin called lipopolysaccharide (LPS). First, the researchers used whole-brain activity mapping to identify which neurons were activated in response to LPS treatment and found that a subset of neurons in the nucleus of the solitary tract (NTS) and the area postrema (AP) were activated.
The researchers then used a genetic technique to selectively activate these neurons in mice. They found that it replicated the sickness behaviors induced by LPS. They also found that inhibiting these neurons diminished the behavioral responses to LPS.
Further analysis using single-nucleus RNA sequencing helped identify a specific group of neurons activated in response to LPS and responsible for the sickness behaviors. These neurons were located in the NTS-AP and expressed a specific gene called ADCYAP1.
The researchers concluded that the pleiotropic effects of LPS on sickness behaviors are controlled by a specific group of neurons in the NTS-AP that are necessary and sufficient for the sickness response. This establishes a critical link between the brain and the body’s response to infection.
This finding is relevant because it helps explain how the body responds to infections and how the brain controls these responses. Understanding the neural mechanisms underlying sickness behaviors may lead to the development of new treatments for infections that target these specific neurons. Additionally, this research may have broader implications for understanding the neural basis of other physiological responses to disease and injury.
