A specific set of neurons in the brain may be responsible for making us feel sick.
The findings could lead to better ways to reverse these symptoms.
When you get an infection, many changes occur in your body. In addition to the activity of the immune system, physiological and behavioral changes occur that help eliminate the infection. These include fever, loss of appetite, heat seeking, and fatigue. These symptoms are governed by the brain, rather than the immune system. But it has not been clear which neurons in the brain control these changes and how they know when the body has been infected.
A team of NIH-funded researchers led by Dr. Catherine Dulac at Harvard University set out to identify which neurons in mouse brains are involved in the response to infections. Their findings appeared in Nature .
To induce the disease, the researchers injected the mice with an inflammatory agent that mimics an infection. In doing so, it activated cells in a part of the hypothalamus called the ventral medial preoptic area (VMPO). The hypothalamus is the region of the brain responsible for regulating functions such as temperature, hunger, and circadian rhythms. The cells that were activated included both neurons and non-neuronal cells . They were located at the base of the brain, near an area where molecules can cross the blood-brain barrier. The neurons had receptors for various immune signals produced by nearby non-neuronal cells.
The team engineered these neurons in mice so that they could be activated by a chemical signal. The activation of the neurons increased the body temperature of the mice and caused them to eat less and seek warmer environments, as if they had an infection. The researchers also tried to selectively kill these neurons. This prevented the mice from developing fever or seeking warmer environments in response to infection.
The team then identified the brain regions to which the VMPO neurons sent signals. They designed these connections in mice to activate when they were illuminated by a particular color of light. Activating connections to a part of the hypothalamus increased body temperature. Activating them in a different part of the hypothalamus reduced the amount the mice ate.
The results suggest that these VMPO neurons act as a hub to coordinate diverse physiological responses to infection. Researchers propose that when an infection generates immune signals in the blood, these trigger the release of signals in the brain by the cells that line the blood-brain barrier. Signals from these cells activate nearby neurons in the VMPO. Activated neurons raise body temperature, drive heat seeking, and reduce appetite.
The findings could potentially lead to ways to reverse the disease’s symptoms when they become dangerous to a person’s health. “If we know how it works, maybe we can help patients who have difficulty with these types of symptoms, like chemotherapy patients or cancer patients, for example, who have a very low appetite but there is really nothing we can do for them. ", says. lead author Dr. Jessica Osterhout.
The researchers plan to further explore where these neurons connect in the brain. They also hope to explore how the neurons might affect other physiological or behavioral changes associated with the disease.
