110. Induction of leukocyte adhesion mediators in the neurovascular unit after repeated social defeat

Abstract

Repeated social defeat (RSD) is a model of psychosocial stress that activates several neuroendocrine pathways resulting in significant physiological, immunological, and behavioral changes. For instance, RSD promotes microglia activation, anxiety-like behavior, and macrophage trafficking to the brain. Although RSD promotes myeloid cell trafficking to brain-specific regions associated with threat and appraisal (i.e., prefrontal cortex, amygdala), the process by which this occurs is unknown. Because microglia and neuronal activation following RSD is region-specific, we hypothesize that adhesion molecule expression on the neurovascular unit facilitates the recruitment of myeloid cells to the brain with stress. Here we show that RSD caused an exposure- and brain region-dependent increase in mRNA of ICAM1 and VCAM1, two key cell adhesion molecules involved in leukocyte trafficking, especially in brain regions associated with fear and anxiety responses. IHC analysis from WT and BM-chimera mice confirmed increases in ICAM1 and VCAM1 protein in the brain after RSD. Next, the mRNA expression of several chemokines, selectins, and MMPs were determined in specific brain areas and revealed robust differences in distinct selectins and chemokines in stressed mice. For example, CXCR2 and its ligands CXCL1 and CXCL2 showed an exposure- and brain-region dependent induction after RSD. Collectively, these data indicate that key adhesion mediators are increased in the brain vasculature following RSD and that the pattern of chemokine expression may underlie the mechanism of macrophage trafficking.