MDNews - Minnesota

SPECIAL CLINICAL SECTION: MENTAL HEALTH New Insights into By Thomas Crocker A MOUSE-MODEL STUDY BY RESEARCHERS FROM THE OHIO STATE UNIVERSITY REVEALED NEW INFORMATION ABOUT THE IMMUNE SYSTEM'S ROLE IN DETERMINING RESPONSE TO STRESS AND MAY POINT THE WAY TOWARD NOVEL TREATMENT STRATEGIES FOR MOOD DISORDERS IN HUMANS. R ESULTS OF THE study were published in The Journal of Neuroscience last August. The researchers' work was grounded in the principles of psychoneuroimmunology, a field that developed more than 20 years ago to investigate how psychological and physiological interactions influence the immune system. "In the 1990s, researchers realized mood disorders seemed to affect immunity, but they weren't sure whether it was a directional or bidirectional process," says John Sheridan, PhD, Professor of Oral Biology at The Ohio State University College of Dentistry, Associate Director of the Institute for Behavioral Medicine Research at The Ohio State University Wexner Medical Center and senior author of the study. "The origin of this work is the belief that one's interpretation of environmental challenges can actually play out through the central nervous system, through the autonomic nervous system, and influence immunity. The really interesting part, as it turns out, is that activation of the immune system can profoundly influence behavior." 18 Development | Twin Cities MD NEWS ■ MDNEWS.COM Sheridan and his colleagues sought confirmation of the bidirectionality of stress reactions — that a response that begins in the brain can prompt certain actions by the immune system, which, in turn, influence behavior. Prolonged Effects of Repeated Defeat The researchers constructed a study model in which they introduced an aggressive male mouse into a cohort of male mice with an established social hierarchy for several nights. The outsider fought the group members and inflicted repeated social defeat on them, causing them to exhibit anxietylike behavior more than a week after their last encounter with the interloper. The mice's anxiety persisted for weeks. "The mice exhibited some real immunological changes," Sheridan says. "Typically, when you stress an animal, a lot of corticosterone and glucocorticoids are released into circulation; those tend to be immunosuppressive and introduce programmed cell death in a lot of cells in the immune system, leading to shrinkage of things such as the thymus and spleen. In these mice, the spleen was huge. Rather than inducing programmed cell death, this model increased the number of cells in the spleen, and it turned out those cells came from the bone marrow." Sheridan characterized the stimulation of the bone marrow as one of the study's most surprising discoveries. "Repeated defeat seemed to encourage innate immunity by stimulating the production and release of granulocytes and monocytes — cells of the innate immune system — from the bone marrow," he says. "From an immunologist's point of view, that was a really exciting finding. Clinicians use drugs that attack or focus on the central nervous system to treat most prolonged anxiety and depressive-like behaviors in humans. What we're saying is there's a peripheral, cellular component that may provide a new target of opportunity for treatment of some of these diseases." ■

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