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dc.contributor.authorMasood, Jaudaten
dc.date2015-08-19 19:20:25.076
dc.date.accessioned2015-08-26T01:31:45Z
dc.date.issued2015-08-25
dc.identifier.urihttp://hdl.handle.net/1974/13527
dc.descriptionThesis (Master, Neuroscience Studies) -- Queen's University, 2015-08-19 19:20:25.076en
dc.description.abstractGastrointestinal (GI) diseases such as inflammatory bowel disease, Hirschsprung’s disease or diabetic gastropareisis result in the loss of enteric neurons. The replacement of these lost neurons could potentially normalize the functional disturbances associated with these diseases. Within the adult enteric nervous system (ENS) there is a population of neural stem cells (NSCs) that appear to proliferate in vitro following dissociation. Until recently enteric neurogenesis in vivo has proven challenging due to the presence of a brake on proliferation. However dissociation of enteric ganglia appears to release this brake. We hypothesized that dissociation induces enteric neurogenesis by disrupting synaptic connections between enteric neurons. Our primary aim was to test this hypothesis and identify which enteric neurotransmitters might be responsible for the suppression of neurogenesis in vivo. Whole-mount preparations of intact longitudinal muscle-myenteric plexus (LMMP) from mouse colon were grown in a 7-day culture protocol. Proliferating cells were visualized by uptake of ethynyl deoxyuridine (EdU) while manipulating neurotransmission. Immunohistochemical analysis of the overlap between EdU-labeled cells and Human D (HuD)-immunoreactive neurons were used as a marker for neurogenesis. Mann-Whitney and Kruskal-Wallis tests were employed to compare population data. Incubation of the LMMP in tetrodotoxin (TTX; 1 μM), which blocks action potential discharge, caused a significant 3-fold increase in myenteric neurogenesis. The muscarinic receptor antagonist scopolamine (1 μM) also significantly enhanced neurogenesis, an effect that was mimicked by inhibiting phospholipase C with U73122 (1 μM). Interestingly, nicotinic receptor antagonists had no effect on neurogenesis. A significant increase in neurogenesis was also observed following inhibition of neuronal nitric oxide synthase by 7-Nitroindazole (30 μM). This nitrergic brake on neurogenesis may be dependent on activation of soluble-guanylyl cyclase as indicated by increased neurogenesis following incubation in oxadiazole quinoxalin (ODQ; 10 μM). Additionally, treatment of LMMP with purinergic receptor antagonist, suramin (100 μM) resulted in increased neurogenesis per ganglia compared to controls. In contrast to nitrergic, purinergic and cholinergic pathways, serotoninergic neurotransmission appears to play no role in modulating neurogenesis. Furthermore, inclusion of the following growth factors, glial derived neurotrophic factor, fibroblast growth factor and epidermal growth factor, in the media for the duration of the culture period prevented excessive death of myenteric neurons in both control and drug-treated cultures. These data suggest that selective enteric neurotransmission suppresses neurogenesis in the adult ENS. Pharmacological manipulation of neurotransmitter pathways regulating neurogenesis may be a viable means of replacing damaged neurons and restoring normal function following GI injury.en
dc.language.isoengen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsQueen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canadaen
dc.rightsProQuest PhD and Master's Theses International Dissemination Agreementen
dc.rightsIntellectual Property Guidelines at Queen's Universityen
dc.rightsCopying and Preserving Your Thesisen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectneuroscienceen
dc.subjectenteric nervous systemen
dc.subjectneurogenesisen
dc.subjectgastrointestinalen
dc.titleNeurotransmission modulates neurogenesis within the postnatal enteric nervous systemen
dc.typethesisen
dc.description.restricted-thesisThis work is not yet published and my supervisor and I request for the thesis to be restricted until that time.en
dc.description.degreeM.Sc.en
dc.contributor.supervisorLomax, Alan E.en
dc.contributor.departmentNeuroscience Studiesen
dc.embargo.terms1825en
dc.embargo.liftdate2020-08-23
dc.degree.grantorQueen's University at Kingstonen


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