Intestinal innervation and its role in mucosal damage and inflammation

The regulatory role of the autonomic nervous system (ANS) in intestinal inflammation and immunity is widely acknowledged. In this thesis, we investigated mediating pathways and demonstrated a pivotal role for the spleen. We studied the effect of electrical splenic nerve bundle stimulation (SpNS) in a mouse model of experimental colitis induced by dextran sulfate sodium and showed that SpNS reduced colitis. Further, we elucidated effects of sympathetic activity on intestinal mucosal homeostasis. Chemical sympathetic denervation through 6-hydroxydopamine led to enhanced intestinal inflammation, and impaired barrier integrity. In contrast, adrenergic receptor stimulation through UK 14,304, a specific receptor agonist, led to increased proliferation and stem cell function. Adrenergic receptor α2A was found to act as molecular delegate of intestinal epithelial sympathetic activity controlling cell proliferation, differentiation, and host defense.
The ANS is a complex network activating numerous pathways and therefore effects can be ambiguous and are often challenging to interpret. Our studies increased the understanding of effects of autonomic neuronal activity on intestinal processes, and future studies should continue investigations with not only experimental, but also clinical research. Ultimately, a role for bioelectronic medicine in intestinal immunity and mucosal healing can be allocated and neuromodulatory techniques are to be examined as a plausible treatment modality.