The role of serotonin in the immunoregulation by the helminth parasite Hymenolepis diminuta

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dc.contributor.advisorMcKay, Derek Mark
dc.contributor.advisorSharkey, Keith A.
dc.contributor.authorWang, Susan Joanne
dc.contributor.committeememberNasser, Yasmin
dc.contributor.committeememberGeuking, Markus B.
dc.date2020-02
dc.date.accessioned2019-12-20T19:00:14Z
dc.date.available2019-12-20T19:00:14Z
dc.date.issued2019-12-19
dc.description.abstractWhile infection with parasitic helminths remains a major concern for a quarter of the worlds’ population in non-westernized societies, the incidence of infection has significantly reduced in westernized societies. Simultaneously, the incidence of autoimmune diseases, such as inflammatory bowel disease, is on the rise in the industrialized-west. Studies of infection with various helminths, including the rat tapeworm, Hymenolepis diminuta, in murine models of inflammatory disease reveal the potential of helminth-based therapeutics. Serotonin (5-hydroxytryptamine, 5-HT) has previously been shown to be responsive to infection with a helminth. It has a variety of immunomodulatory actions in the gastrointestinal tract, yet its potential role in helminth expulsion and helminth therapy is largely unknown. Thus, the research presented in this thesis sought to test the hypothesis that infection with H. diminuta evokes increases in mucosal serotonin levels, important for fine-tuning type 2 (Th2) immunity and are involved in H. diminuta-mediated inhibition of dinitrobenzene sulphonic acid (DNBS)-induced colitis. Three specific aims were: (1) assess changes in murine intestinal serotonin following infection with H. diminuta, (2) determine if serotonin was important in the expulsion of H. diminuta from its non-permissive mouse host; and, (3) evaluate if manipulation of the enteric serotonergic system affected H. diminuta-evoked suppression of murine colitis caused by DNBS. This study did not find evidence of an increase in serotonin in the small intestine of H. diminuta-infected male BALB/c mice, and the extrinsic manipulation of the serotoninergic system via systemic delivery of a tryptophan hydroxylase inhibitor (para-chlorophenylalanine), 5-HT7 receptor antagonist (SB269970), or selective serotonin reuptake transporter inhibitor (fluoxetine) had negligible effects on worm expulsion or systemic Th2 events post-infection. Thus, the data do not support the hypothesis that enteric serotonin is a major influence of the immune response to infection with H. diminuta. Preliminary findings, however, suggest that the stress response to consecutive daily handling and i.p. injections may abrogate the helminth-evoked suppression of DNBS-induced colitis in mice, highlighting the neuro-immune axis and stress component of experimental design when studying inflammatory disorders.en_US
dc.identifier.citationWang, S. J. (2019). The role of serotonin in the immunoregulation by the helminth parasite Hymenolepis diminuta (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/37358
dc.identifier.urihttp://hdl.handle.net/1880/111367
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectserotoninen_US
dc.subjecthelminthen_US
dc.subjectenteroendocrineen_US
dc.subjectTh2 immunityen_US
dc.subjectIBDen_US
dc.subjecthelminth therapyen_US
dc.subjectmouse modelen_US
dc.subjectinflammationen_US
dc.subject.classificationPhysiologyen_US
dc.titleThe role of serotonin in the immunoregulation by the helminth parasite Hymenolepis diminutaen_US
dc.typemaster thesisen_US
thesis.degree.disciplineMedicine – Gastrointestinal Sciencesen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameMaster of Science (MSc)en_US
ucalgary.item.requestcopytrueen_US
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