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dc.contributor.authorGondora, Nyasha
dc.date.accessioned2020-04-14 17:01:34 (GMT)
dc.date.available2020-04-14 17:01:34 (GMT)
dc.date.issued2020-04-14
dc.date.submitted2020-03-30
dc.identifier.urihttp://hdl.handle.net/10012/15751
dc.description.abstractCrosstalk between receptors allows for the integration of diverse and complex signalling pathways. Transactivation is a form of crosstalk between G-protein coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). RTKs are transactivated by GPCRs through two main mechanisms: ligand- independent intracellular pathways and triple membrane passing mechanisms involving GPCR mediated growth factor signaling. Transactivation has neuroprotective potential; however, the physiological relevance of this pathway is not known. Interestingly, some stressors can up- or downregulate GPCR and RTK activity, as well as initiate certain transactivation pathways, leading to the question: could transactivation be a stress response? Given the impact of stress on GPCRs and RTKs, this thesis directly explored the impact of stress, more specifically acute chemical stress, in the form of the stress hormone corticosterone and chronic stress, in the form of Chronic Early Life Social Isolation (CELSI), on the 5HT7-TrkB transactivation pathway. Another aim of this thesis was to analyze the effect of social isolation (CELSI) on the expression of proteins that are implicated in neuroplasticity and to explore if social isolation stress differentially primes the brain's response to stress or other stimuli. Coupling cell line based experiments with ex vivo tissue work, the overall aim of this thesis research was to gain a better understanding of some molecular mechanisms underlying the impact of stress on the brain.en
dc.language.isoenen
dc.publisherUniversity of Waterlooen
dc.subjectG-protein coupled receptors (GPCRs)en
dc.subjectReceptor tyrosine Kinases (RTKs)en
dc.subjectTrkBen
dc.subjectBDNFen
dc.subjectNMDAen
dc.subjectGluN2Ben
dc.subjectstressen
dc.subjectChronic early life social isolation (CELSI)en
dc.titleGPCR and RTK Regulation in Neurons: The Impact of Stress on GPCR and RTK signalling and Crosstalken
dc.typeDoctoral Thesisen
dc.pendingfalse
uws-etd.degree.departmentSchool of Pharmacyen
uws-etd.degree.disciplinePharmacyen
uws-etd.degree.grantorUniversity of Waterlooen
uws-etd.degreeDoctor of Philosophyen
uws.contributor.advisorBeazely, Michael
uws.contributor.advisorMielke, John
uws.contributor.affiliation1Faculty of Scienceen
uws.published.cityWaterlooen
uws.published.countryCanadaen
uws.published.provinceOntarioen
uws.typeOfResourceTexten
uws.peerReviewStatusUnrevieweden
uws.scholarLevelGraduateen


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