Please use this identifier to cite or link to this item: http://theses.ncl.ac.uk/jspui/handle/10443/2705
Title: Ageing in the zebrafish heart
Authors: Burns, David
Issue Date: 2014
Publisher: Newcastle University
Abstract: With advancing age there is a progressive decline in the function of the heart. In humans reductions in stroke volume and cardiac output occurs often resulting in cardiac disease and subsequent death. The pathology found in the heart due to advancing age is attributed to a reduction in cardiomyocytes which causes cardiac dysfunction and heart disease, leading to heart failure. Zebrafish are a valuable tool in studying ageing and heart disease. As zebrafish age they gradually senesce. This is similar to humans and other mammals. However the response of the zebrafish heart to ageing has not been explored. The zebrafish heart changes due to ageing, with increased fibrosis and ventricular wall thickness. I have established new assays to measure proliferation and apoptosis in zebrafish cardiomyocytes using multiplexing of thymidine analogues and cleaved caspase 3, respectively. Using these developed assays it was discovered that these changes may be caused by an observed increase in cardiomyocyte apoptosis. This was coupled with no change in cardiomyocyte proliferation. These changes may be mediated by an increase in natriuretic peptide expression. In response to exercise, cardiomyocyte proliferation increases signalled by increased gata4, nkx2.5, tbx5, and mef2c expression and a reduction of natriuretic peptide expression. In the long term these genetic and cellular changes in the heart in response to exercise may slow some of the pathological changes observed in the heart.
Description: PhD Thesis
URI: http://hdl.handle.net/10443/2705
Appears in Collections:Institute of Genetic Medicine

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