THE ROLE OF MAST CELLS IN GUT PHYSIOLOGY, BRAIN CHEMISTRY, AND BEHAVIOUR

Abstract

Background and Research Aim: Stress affects the immune system, which influences host physiology. Mast cells have been associated with several stress-induced changes in gut physiology. Mast cells also have the potential to influence the brain and behaviour. We investigated how mast cells influenced the body, brain, and behaviour during stress. Methodology: We investigated the behaviour of mast cell deficient animals and deficient animals that received whole bone marrow (WBM) transplants. We also studied the effects of mast cell stabilization during stress on changes in gut motility, via ex vivo. recordings of intestinal segments, and brain, via behavioural measurements and flow cytometry analysis of proinflammatory monocyte trafficking to the brain. Results: Mast cell deficiency leads to several behavioural changes related to activity level, exploration, and sociability. Furthermore, deficient animals that received WBM transplants demonstrated social and anxiety-like behaviour that differed from their deficient counterparts. Mast cell stabilization during stress prevented many of the stress-induced changes in gut motility commonly observed in the intestine. Mast cell stabilization during stress also prevented proinflammatory monocyte trafficking to the brain and was associated with reduced anxiety-like behaviour. Conclusion: Our findings support the role of mast cells in baseline behaviour, suggesting the presence of mast cells is needed for normal social and anxiety-related functioning. We also found that mast cell activation contributes to stress-induced intestinal dysmotility, suggesting that mast cells should be a target for interventions of stress-related gut motility disorders, such as irritable bowel syndrome. Lastly, our findings on the role of mast cells in monocyte trafficking and anxiety adds to our knowledge of neuroimmune interactions during stress and supports a potential role for mast cells in anxiety-related mood disorders, where stabilization of mast cells during stressful events may be of benefit.