Localising NMDA receptors in human platelets and evaluating significance of anti-platelet antibodies in stroke patients

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dc.contributor.advisor Kalev-Zylinska, M en
dc.contributor.author Park, Young Eun en
dc.date.accessioned 2012-07-16T02:49:53Z en
dc.date.issued 2012 en
dc.identifier.uri http://hdl.handle.net/2292/19340 en
dc.description Full text is available to authenticated members of The University of Auckland only. en
dc.description.abstract Glutamate represents one of the most important chemical signalling compounds in the central nervous system but not much is known about it outside of the brain. Increasing research indicates that glutamate and its receptors contribute to the functioning of peripheral tissues, including megakaryocytes and platelets. The main objective of this study was to characterise NMDA receptor expression in human platelets using flow cytometry and electron microscopy. Flow cytometry confirmed previous data obtained in this laboratory that NMDA receptor subunits: GluN1, GluN2A and GluN2D are present in platelets. The surface expression of GluN1 was low in resting platelets but increased after platelet activation with ADP. Permeabilisation procedure allowed increased amounts of GluN1, GluN2A and GluN2D to be detected in platelets, suggesting significant intracellular storage pools of these proteins, as in neurons. High-resolution electron microscopy was used to investigate sub-cellular localisation of NMDA receptor subunits in platelets. GluN1, GluN2A and GluN2D were detected within alpha and dense granules, open canalicular systems, underneath and on the surface of plasma membranes, and on platelet projections. In resting platelets, majority of the subunits were found intracellularly, including in granules and channels; whereas in activated platelets GluN proteins were frequently seen on platelet surfaces and projections. Expression of GluN proteins at points of contact between platelets suggests that NMDA receptors may convey signals during platelet-platelet interactions. The second part of this thesis evaluated the presence of anti-platelet antibodies in stroke patients, and sought clinical correlations. Stroke patients were found to have higher incidence of platelet-reactive antibodies, compared with healthy blood donors. Clinically, stroke patients who had anti-platelet antibodies were more likely to have larger strokes with more severe neurological deficit. Intriguingly, patients with antibodies showed better recovery from their presenting deficit, suggesting that anti-platelet antibodies induce functional effects in vivo. In support of the in vivo antibody functionality, antibody-positive patients had higher platelet counts, suggesting an increased compensatory platelet production. Contrary to our original hypothesis, others in the laboratory found no evidence that stroke antibodies target GluN1. Further work is required to identify antibody targets and elucidate NMDA receptor function in human platelets. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof Masters Thesis - University of Auckland en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights Restricted Item. Available to authenticated members of The University of Auckland. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/nz/ en
dc.title Localising NMDA receptors in human platelets and evaluating significance of anti-platelet antibodies in stroke patients en
dc.type Thesis en
thesis.degree.grantor The University of Auckland en
thesis.degree.level Masters en
dc.rights.holder Copyright: The author en
pubs.author-url http://hdl.handle.net/2292/19340 en
pubs.elements-id 358400 en
pubs.org-id Academic Services en
pubs.org-id Examinations en
pubs.record-created-at-source-date 2012-07-16 en

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