Immune cells activated during a state of chronic stress seem to end up on standby in the spleen to be saved for later use, according to a new mouse study by researchers at Ohio State University. This may trigger an exaggerated stress reaction to a single event much later, launching the body back into a state of chronic stress.
The excessive immune response and anxiety later triggered by a brief stressor mimic symptoms of post-traumatic stress disorder.
During the study, researchers found that even after mice had recovered from a state of chronic stress, they quickly returned to that state after experiencing a single stressful event 24 days later. Mice that had not experienced the chronic stress were unaffected by the single stressful event.
Mice without spleens did not experience the same reaction to the single stressor. This suggests that the spleen is used as a reservoir for primed immune cells until they’re activated to response to another stressor.
“No one else has done a study of this length to see what happens to recovered animals if we subject them again to stress,” said Jonathan Godbout, Ph.D, a lead author of the study and associate professor of neuroscience at Ohio State.
“That retriggering is a component of post-traumatic stress. The previously stressed mice are living a normal rodent life, and then this acute stress brings everything back. Animals that have never been exposed to stress before were unaffected by that one event — it didn’t change behavioral or physiological properties.”
In this model of stress, an aggressive male mouse was added to a group of other male mice that had already been given time to establish a hierarchy. For two hours at a time, the aggressive mouse repeatedly defeated the resident mice. After six days, this social defeat led to an inflammatory immune response and anxiety-like behavior.
The researchers then removed the spleens of some of the chronically stressed mice. After spleen removal, the stress-sensitized mice were no longer sensitive to the single stressor and the re-establishment of anxiety.
The scientists also detected no immune cell trafficking to the brain or anxiety-like behavior. This suggests that the spleen is the source of immune cells that respond to the single stressor.
“Our colleagues who study behavior talk about sensitization,” Sheridan said. “Clearly, the repeatedly stressed mice were sensitized. What we’re adding is that sensitization is associated with a specific cell type that resides in the spleen after the initial sensitization.”
“The key is those cells. They originate in the bone marrow, but in terms of sensitization, the spleen is a significant organ.”
Sheridan added that other researchers are testing blood samples of PTSD patients for biomarkers such as immune cells or pro-inflammatory proteins that could reveal which patients are in a stress-sensitized state.
The research is published online in the journal Biological Psychiatry.
Additional co-authors, all from Ohio State, include Eric Wohleb, Daniel McKim, Daniel Shea, Nicole Powell, and Andrew Tarr.