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EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON DORSAL VAGAL COMPLEX NEURONS THAT EXERT REFLEX CONTROL OF THE GASTROINTESTINAL TRACT

Emch, Gregory Simon

Abstract Details

2002, Doctor of Philosophy, Ohio State University, Neuroscience.
The results of the experiments presented in this thesis have shown that injection of tumor necrosis factor-alpha (TNF) into the dorsal vagal complex [DVC; made up of the area postrema (AP), the sensory nucleus of the solitary tract (NST), and the dorsal motor nucleus of the vagus (DMN)] has mixed results on neuronal activity in this medullary brainstem area. In the NST, microinjection of TNF causes a significant and dose-dependent increase in neuronal firing rate (FR) as compared to injection of saline controls. Subsequently, some NST neurons exhibit a potentiated response to afferent stimulation following pre-exposure of the neurons to TNF. Conversely, microinjection of TNF significantly inhibits the FR of most neurons in the DMN. Immunohistochemical studies show that the protein product of the proto-oncogene c-Fos (a marker of neuronal activation) is increased in response to systemic administration of lipopolysaccharide (LPS; bacterial cell coat component that induces endogenous production of TNF) in the DVC. Additionally, protein expression is independent of the integrity of the vagus nerve(s). That is, surgical section of the vagi does not inhibit the increase in number of c-Fos labeled neurons. Direct injection of TNF into the NST causes a significant elevation of Fos-labeled neurons, and protein expression is dependent on glutamate neurotransmission since glutamate receptor antagonists abolish any significant increase in Fos-positive neurons evoked by injection of TNF alone. Therefore, it was concluded that tumor necrosis factor-alpha causes gastrointestinal stasis by removing cholinergic excitation to the stomach. TNF alters vago-vagal reflexes by acting directly on neurons at the level of the dorsal vagal complex in the medullary brainstem.
Georgia Bishop (Advisor)

Recommended Citations

Citations

  • Emch, G. S. (2002). EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON DORSAL VAGAL COMPLEX NEURONS THAT EXERT REFLEX CONTROL OF THE GASTROINTESTINAL TRACT [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1018475175

    APA Style (7th edition)

  • Emch, Gregory. EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON DORSAL VAGAL COMPLEX NEURONS THAT EXERT REFLEX CONTROL OF THE GASTROINTESTINAL TRACT. 2002. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1018475175.

    MLA Style (8th edition)

  • Emch, Gregory. "EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON DORSAL VAGAL COMPLEX NEURONS THAT EXERT REFLEX CONTROL OF THE GASTROINTESTINAL TRACT." Doctoral dissertation, Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu1018475175

    Chicago Manual of Style (17th edition)