Disturbances of gastrointestinal (GI) motility are characteristic of enteric parasitic infections as well as enterotoxigenic and invasive enteric bacterial infections. These motility disturbances are a frequently suspected but poorly understood cause of GI symptoms producing considerable distress and morbidity in animal and human hosts. Yet, the underlying physiological mechanisms which alter motility during enteric parasitism are unknown. The long-term objective of this project is to elucidate the role of the enteric nervous system in the onset and maintenance of alterations of intestinal motor patterns during enteric parasitic infection.
The specific aim i s to characterize the effects of parasitic infection on the physiology of the enteric nervous system or guinea-pigs infected with the nematode, Trichinella spiralis. The rationale is that alterations of gut motility during parasitism are mediated through inflammatory and immunological reactions which transduce signals through neural pathways in the enteric nerve plexuses which coordinate activity of the intestinal musculature. The effects of parasitic infection on enteric nervous system function will be assessd by intracellular electrophysiological recording techniques. These methods will be used to examine: (1) the electrical behavior and synaptic circuitry of neurons from enteric ganglia of small intestine of non-immune and immune animals during infection with T. spiralis; (2) changes in chemical neurotransmissions during infection by assessing responsiveness to exogenously applied neurotransmitters and chemical mediators of inflammation and anaphylaxis; and (3) the effects of application of parasites and parasite antigens to an intact mucosa-nerve preparation in order to investigate relations between the process of parasite establishment and the induction of inflammation and immunological responsiveness in the gut with altered enteric nervous system function. This approach will provide more definitive information on the physiological mechanisms responsible for intestinal motor disturbances during enteric parasitism, and it will greatly expand our understanding and insight into the causes of GI motility disorders which occur during allergic and inflammatory disease states in the intestine in general. In a broader context, these studies will be the first to address the interactions between the nervous and immune systems in terms of integrative function.
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