Duke Health researchers found a relationship between immune response and neurological behavior after studying mice with a specific gene mutation, which exhibited signs of ADHD in response to an antiviral mechanism.
The study, which was published in the Brain, Behavior and Immunity journal in November, was led by Anthony Filiano, assistant professor in neurosurgery, integrative immunobiology and pathology at the School of Medicine and faculty member at the Marcus Center for Cellular Cures. It was conducted in collaboration with researchers at Columbia University and the National Institutes of Health.
Filiano explained that previous research has shown that certain maternal infections are associated with neurodevelopmental disorders, like attention-deficit/hyperactivity disorder (ADHD) and autism. However, he said that the link between the body’s natural immune response and such disorders is largely “unclear.”
So, Filiano and his team decided to study molecules called interferons that are an important part of the body’s antiviral response. They knew that interferons could regulate neural circuits and neuron activity, and they had found in a prior study that neurons responded differently to interferons than other cells did.
“Typically, when cells receive interferons — like when you get a viral infection — the pathway is activated really quick, and then it’s shut down quickly as well. And that’s so you can have antiviral activity without all of this collateral damage,” Filiano said. “We found that neurons have this very unique, prolonged response, which is very surprising.”
To examine this interferon-neuron pathway — known as an interferon-induced STAT1 signaling pathway — further and see whether prolonged signaling could impact behavior, Filiano and his colleagues created a transgenic mouse model, meaning they bred mice with a specific gene mutation.
After the researchers over-activated the immune response pathway in different cells in the mice’s brains, the mice exhibited hyperactivity in a way that represented the criteria for ADHD.
“Historically, it has been thought that the brain and the immune system were two separate systems, but now we find that there's a lot of interaction between the two,” Filiano said. “I think we've just really cracked the surface [of] understanding how each of the systems can impact each other.”
Filiano explained that the clinical mutation they used to create the mice exists naturally in humans as well, albeit in rare cases.
“There’s people in this world walking around with this mutation, and they have a lot of immune problems,” he said.
As a result, this research has implications for designing better treatments for people with the STAT1 signaling pathway mutation, as well as for those with broader neurological conditions.
For future work, Filiano discussed attempting to better understand the unique relationship between neurons and interferons, which could help improve the precision of new treatments.
“There's a lot of FDA-approved drugs to target the interferon pathway, but what I think is challenging is targeting the right cell types, like it's really hard to target neurons,” he said. “… You don’t want to just completely block or target these immune pathways because they do have antiviral function and anti-cancer, anti-tumor function. So, we have to use a scalpel approach and not a sledgehammer approach.”
Get The Chronicle straight to your inbox
Signup for our weekly newsletter. Cancel at any time.
Srilakshmi Venkatesan is a Trinity first-year and a staff reporter for the news department.