The Surprising Brain-immune Connection
Growing up in a traumatic or abusive environment can trigger toxic stress — a prolonged, severe stress response that can impair brain function. Without appropriate help and support, children living in these situations often have trouble learning and controlling their behavior.
Ning Quan, Ph.D., professor of biomedical science in the Charles E. Schmidt College of Medicine, and Randy D. Blakely, Ph.D., also a professor of biomedical science and executive director of the Stiles-Nicholson Brain Institute, are zeroing in on a surprising way that stress affects the developing brain — through the immune system.
Throughout the body, the IL-1 receptor triggers inflammation by binding to the immune cytokine IL-1, a signaling molecule. But research has shown that the receptor is also expressed in the brain. Looking more closely, Quan found that the receptor is present at different levels in specific mouse neurons during normal development — in the absence of inflammation or infection — suggesting it has an important part to play in shaping the brain.
“Our research suggests that the IL-1 receptor, which was initially thought to be involved in the immune response against bacteria or viruses, is actively involved during neurodevelopment,” Quan said. “It reshapes the circuitry for you to adapt to the outside world.”
Quan’s work also shows that the receptor is important in the stress response. When mouse pups are stressed, such as when they are taken away from their mothers for a period of time, IL-1 receptor levels rise, and the pups show signs of anxiety. When Quan’s team stops the receptor from working, the pups cope much better. The results suggest that it’s possible to make mouse pups, and perhaps human children, more resilient by targeting this receptor.
The research revealed that neurons that release serotonin, a neurotransmitter associated with mood and anxiety, also express the IL-1 receptor in stressful situations. As an expert in neurotransmitter release, Blakely is now working with Quan to look at the association between the IL-1 receptor and serotonergic neurons. “If you take away that inflammatory molecule from the serotonergic neurons selectively, our data indicate that it is unable to carry an echo of that trauma into the future,” Blakely said. “So, it’s a very important signaling molecule network that we think has a lot to say about early life stress.”