Talk abstracts

Talk on Wednesday 03:00-03:15pm submitted by Eric Wohleb

Acute social defeat promoted anxiogenic macrophage recruitment into the brains of sensitized mice

Eric S. Wohleb (Neuroscience, The Ohio State University), Yan Huang (Institute for Behavioral Medicine Research, The Ohio State University), Daniel T. Shea (Oral Biology, The Ohio State University), Dan B. McKim (Neuroscience, The Ohio State University), Andrew J. Tarr, Nicole D. Powell (Oral Biology, The Ohio State University), John F. Sheridan (Oral Biology, The Ohio State University)

Abstract:
Repeated social defeat (RSD) is a murine stressor that recapitulates several key physiological, immunological, and behavioral alterations that are observed in humans exposed to psychosocial stressors. Although previous results show that RSD-induced activation of brain CD11b+ cells (microglia/macrophages) contribute to the development of anxiety-like behavior, their role is not defined in prolonged anxiety-like behavior. Thus, the objective of this study was to determine the extent to which brain CD11b+ cells maintain an inflammatory profile and contribute to prolonged anxiety-like behavior after RSD. Exposure to RSD increased circulating monocytes and caused recruitment of macrophages into the brain that was diminished 24 days after RSD. GFP+ bone marrow chimeric mice confirmed that RSD promoted macrophage recruitment in the brain and that there was a significant reduction in the number of GFP+ macrophages 24 days later. Corresponding to macrophage recruitment in the brain, RSD-induced anxiety-like behavior was evident 8 days after cessation of RSD, but returned to baseline by 24 days. Because stress-induced alterations were not evident after 24 days, the extent to which RSD sensitized stress responses was determined. Mice were sensitized (RSD) and then exposed to acute social defeat 24 days later. Acute stress exposure in sensitized mice significantly increased circulating monocytes, promoted recruitment of macrophages in the brain, and re-established anxiety-like behavior. This is relevant because none of these responses were observed in naïve mice exposed to acute social defeat. These results demonstrated that prior RSD exposure sensitized mice to an acute stressor causing macrophage recruitment into the brain and anxiety-like behavior. These findings implicate macrophage recruitment into the brain as a key intermediate in stress-induced anxiety disorders and provide insight into the cellular mechanisms that promote re-occurrence of anxiety-like behavior.

Keywords: Stress, Mood Disorders, Neuroinflammation