The broad research objectives to be achieved are to enhance knowledge on the underlying mechanisms of brain-gut interactions and how its related to pathophysiology. The hypotheses to be tested, based on our previous work, are; (1) that medullary thyrotropin releasing factor (TRH) is involved in the vagal regulation of gastric function; (2) that brain corticotropin releasing factor, (CRF), mediates stress-induced dysfunction of gastric and colonic transit; (3) that the immune system influences gastric function through the central action of interleukin-1 (IL-1). This will be achieved in rats by combined approaches: immuno- histological: expression of c-fos-like immunoreactivity in brain nuclei in response to stress; molecular: changes in TRH mRNA and CRF mRNA by in situ and Northern blot in medullary neurons in response to external and visceral stimuli influencing vagal activity; neuropharmacological: microinjection of peptide agonists and antagonists at selective activated brain sites; and electrophysiological: recording of efferent discharges in the gastric branch of the vagus. Gastric acid function as well as colonic transit will be investigated. A correlation between the behavioral (fear, anxiety or arousal) and the stimulation of colonic transit induced by CRF at responsive brain sites will be evaluated. This study will yield important information on the neuroanatomic and biochemical substrata involved in the vagal regulation of gastric function and stress-related alterations of gastric and colonic motor activity which may have a bearing on a subset of patients with psychiatric illness (anxiety, depression) and the exacerbation of irritable bowel symptoms induced by stress.
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