Durham Reporter

Researchers at Duke Health have made a connection between immune responses and neurobehavioral conditions, identifying a key infection-fighting function that triggers hyperactive behaviors in mice. The study, published in the journal Brain, Behavior, and Immunity, focuses on STAT1, an on-off switch for genes that plays a significant role in the immune system's response to infections and is linked to neurodevelopmental disorders like autism and ADHD.

Anthony Filiano, Ph.D., senior author of the study and assistant professor at Duke University School of Medicine, highlighted the importance of this discovery: “A lot of these pathways that have been discovered in the immune system also play important roles in the brain,” he said. He noted the robust communication between the immune system and brain as intriguing due to its potential for targeted therapies.

Filiano's team collaborated with researchers at Columbia University to breed mice with a STAT1 mutation. This allowed them to over-activate the immune pathway in various brain cell types, including dopamine neurons involved in reward, motivation, and motor control. Filiano explained: “Prolonged STAT1 signaling in neurons, beginning during embryonic development, led to hyperactive behavior and fewer neurons and reduced neural activity in an area of the brain involved in learning, memory, reward and motivation.”

The findings suggest that STAT1 signaling plays a role in regulating behavior and its disruption may contribute to neurodevelopmental disorders. Filiano mentioned future research would focus on targeting the STAT1 pathway with therapies: “We need to understand its function and target it more specifically before we move forward,” he stated.

The study was authored by Danielle N. Clark, Shelby Brown, Li Xu, Rae-Ling Lee, Joey V. Ragusa, Zhenghao Xu, Joshua D. Milner alongside Filiano. It received funding from several sources including the National Institutes of Health (NS123084), Marcus Foundation, and NIAMS intramural research program.