Abstract # 2044 Glucocorticoids mediate stress-induced upregulation of the alarmin HMGB1 and downregulation of the inhibitory receptor CD200R1 in hippocampus and amygdala: A mechanism of neuroinflammatory priming

Glucocorticoids (GCs) have universally been considered anti-inflammatory. However, mounting evidence now demonstrates that GCs can exert paradoxical effects on innate immune function. In the context of stress exposure, GCs have been found to mediate stress-induced priming of neuroinflammatory responses to subsequent immune challenges. Recent evidence from our laboratory suggests that the alarmin HMGB1 as well as the microglial inhibitory receptor CD200R1 play a causal role in stress-induced neuroinflammatory priming. Here, we explored whether GCs mediate the effects of stress on HMGB1 and CD200R1. Male Sprague-Dawley rats were injected (SC) with vehicle or the GC receptor antagonist RU486 (50 mg/kg). 24 h after injection, rats were exposed to inescapable tailshock (IS) or served as home cage controls (HCCs). Stress exposure increased HMGB1 levels, while decreasing CD200R1 levels in hippocampus and amygdala. Treatment with RU486 blocked these effects of stress on HMGB1 and CD200R1. To examine whether GCs are sufficient to induce these changes in HMGB1 and CD200R1 expression, rats were injected (SC) with vehicle or corticosterone (2.5 mg/kg), which recapitulates the pattern of the GC response to stress exposure. 2 h after injection, corticosterone treatment decreased CD200R1 expression and increased HMGB1 levels. The present results suggest that GCs mediate the effects of stress on HMGB1 and CD200R1, which provides insight into the mechanisms by which stress-induced GCs prime neuroinflammatory processes to subsequent immune challenges.