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dc.contributor.authorGolod, Michael
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date.accessioned2018-06-27T18:03:57Z
dc.date.available2018-06-27T18:03:57Z
dc.identifier.urihttp://hdl.handle.net/1974/24287
dc.description.abstractInsufficient blood flow to the brain generates widespread neurological damage, yet not all brain regions are similarly vulnerable to ischemic injury. During stroke, failure of the Na+/K+-ATPase generates a robust anoxic depolarization that silences neurons in higher brain regions such as the neocortex, whereas the brainstem is capable of recovery and is therefore less sensitive to ischemic damage. The alpha subunit of the Na+/K+-ATPase is primarily responsible for the ion transport rate, particularly the α1 and α3 isoforms which are expressed in neurons. Based on prior evidence that α3 isoform mRNA expression is proportionally greater in the brainstem whereas α1 isoform mRNA expression predominates in higher brain regions such as the neocortex and cerebellum, this study used immunoblotting to investigate the distribution of Na+/K+-ATPase α1 and α3 isoform proteins in the mouse and rat brain. It was determined that α1 isoform expression is higher in the neocortex and cerebellum, whereas α3 isoform expression is higher in the brainstem. In addition, the striatum and hippocampus express similar amounts of both the α1 and α3 isoforms of the Na+/K+-ATPase, although this may be due to a heterogeneous isoform distribution pattern as suggested by pilot immunohistochemical experiments. To assess whether elevated oxidative stress generates adaptive changes in Na+/K+-ATPase expression, isoform distribution was studied in the Aldh2-/- mouse model of oxidative stress, as well as in mice subjected to a chronic unpredictable stress protocol. No changes in Na+/K+-ATPase isoform expression were detected in these cohorts, except for a small but significant decrease in α1 isoform expression in the cerebellum of chronically-stressed Aldh2-/- mice compared to unstressed wild-type mice. To assess whether transient ischemia generates adaptive changes in Na+/K+-ATPase expression, isoform distribution was studied in rats subjected to 90 minutes of middle cerebral artery occlusion followed by 24 hours of recovery. Pilot immunoblotting experiments suggested an increase in the expression of both α1 and α3 isoforms of the Na+/K+-ATPase in the infarcted striatum, indicating that the Na+/K+-ATPase may be implicated in selective neuronal vulnerability to ischemia, but not oxidative stress. This may help identify molecular targets for improving higher brain survival post stroke.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesCanadian thesesen
dc.rightsQueen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada*
dc.rightsProQuest PhD and Master's Theses International Dissemination Agreement*
dc.rightsIntellectual Property Guidelines at Queen's University*
dc.rightsCopying and Preserving Your Thesis*
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.*
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectNa+/K+-ATPaseen_US
dc.subjectAnoxic Depolarizationen_US
dc.subjectStrokeen_US
dc.subjectIschemiaen_US
dc.subjectAlpha Isoformen_US
dc.subjectOxidative Stressen_US
dc.subjectChronic Unpredictable Stressen_US
dc.subjectSelective Vulnerabilityen_US
dc.titleRegional Differences in Na+/K+-ATPase Expression in the Mouse and Rat Brainen_US
dc.typethesisen
dc.description.degreeMaster of Scienceen_US
dc.contributor.supervisorAndrew, R. David
dc.contributor.supervisorBennett, Brian M.
dc.contributor.departmentNeuroscience Studiesen_US


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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
Except where otherwise noted, this item's license is described as Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada