Cal-protectin(g) the brain: dynamics & mechanisms of colitis-induced neuroinflammation 3283

Abstract Description Inflammatory bowel diseases (IBDs) are widespread and on the rise. Interestingly, IBD patients suffer from adverse mental health symptoms more than the general population. Despite this, little is known about how chronic, relapsing intestinal inflammation influences the brain. Investigating neuroinflammation specifically, we have observed that colitis induces an increase in brain calprotectin levels that precedes brain neutrophil infiltration. The calprotectin appears to be produced by a non-immune brain cell population; thus, we hypothesize it may act in recruiting the neutrophils, which appear to be more immature & inactivated than naive neutrophils. Future studies will pinpoint the source & contribution of calprotectin to immune cell recruitment and further phenotype the infiltrating neutrophils. We’ve also observed that colitis alters bone marrow hematopoiesis. As neutrophils originate from the bone marrow, we propose these changes to progenitor cells as a mediator of gut-to-brain inflammation during colitis. We intend to examine the persistence of these changes and investigate their sufficiency to induce similar neuroinflammation as colitis. This work will shed light on the under-investigated immunological connection between intestinal disease & the brain, analyzing the mechanisms by which the inflamed gut & brain communicate. It will lay the groundwork for novel therapeutics targeting IBD-associated behavioral symptoms for which there are no specific treatments currently. Funding Sources NIH T32NS115664-04 Topic Categories Neuroimmunology (NEUR)