DESCRIPTION (provided by applicant): The motor disturbances that are present during inflammation of the bowel reflect a significant interaction between inflammatory mediators and the enteric nervous system. The neural mechanisms of inflammation-induced dysmotility are currently unknown. Using a guinea pig model of experimental colitis, the specific aims of this proposal are to test two hypotheses. The first hypothesis is that inflammation causes an increased excitability in intrinsic primary afferent neurons, which leads to an imbalance in the peristaltic reflex circuit. This hypothesis will be explored by addressing two questions: 1) Do the electrical or synaptic properties of functionally identified myenteric neurons change during experimental colitis? 2) Is the neurogenic propulsive motor activity of the intact guinea pig colon altered during inflammation? The second hypothesis is that changes in the peristaltic reflex circuit, induced by inflammation, persist following histopathological recovery. To test this hypothesis two question will be addressed: 1) Do changes in the electrical or synaptic properties functionally identified myenteric neurons persist or arise following histological recovery from inflammation: 2) Do changes to the neurogenic propulsive motor activity of the intact colon persist or arise following recovery from inflammation? In conducting these studies, we will implement integrated combinations of techniques, including intracellular recording and labeling of neurons, retrograde axonal tracing, immunohistochemistry, and motility assays. These results will advance our understanding of the mechanisms of neuro-immune integration and motility disturbances associated with inflammatory bowel disease and functional bowel disorders.
|Effective start/end date||9/1/01 → 8/31/03|
- National Institute of Diabetes and Digestive and Kidney Diseases: $40,196.00
- National Institute of Diabetes and Digestive and Kidney Diseases: $46,192.00
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