THESIS
2019
xv leaves, 108 pages : color illustrations ; 30 cm
Abstract
Cardiovascular disease is one of the main causes of premature death in humans, and it was
reported to be the primary cause of death in the U.S. during 2018. It has been well established
that cardiovascular events have a specific temporal pattern, and that the circadian rhythm can
influence heart function. For example, death caused by acute myocardial infarction peaks in
morning and late afternoon, rather than being spread evenly throughout the day/night. Thus,
the development of novel chronotherapies might help to alleviate the progression and
consequences of heart disease. Zebrafish have multiple advantages for studying heart
development and function, as well as the circadian clock. For example, they can survive
without a functional cardiovascular system during early developmen...[
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Cardiovascular disease is one of the main causes of premature death in humans, and it was
reported to be the primary cause of death in the U.S. during 2018. It has been well established
that cardiovascular events have a specific temporal pattern, and that the circadian rhythm can
influence heart function. For example, death caused by acute myocardial infarction peaks in
morning and late afternoon, rather than being spread evenly throughout the day/night. Thus,
the development of novel chronotherapies might help to alleviate the progression and
consequences of heart disease. Zebrafish have multiple advantages for studying heart
development and function, as well as the circadian clock. For example, they can survive
without a functional cardiovascular system during early development, thus allowing extensive
experimental intervention. Moreover, the endogenous circadian clock of the zebrafish heart
is directly light‐responsive. Currently, little is known regarding the regulation of the zebrafish
embryonic heart beat rate by the circadian clock. In this project, AB wild‐type, as well as
transgenic Tg ((gal4)cmlc2:GFP) and Tg (per3:luc) lines of zebrafish were raised under three
distinct lighting conditions: constant light (LL), constant darkness (DD), and a normal 12‐h
light/12‐h dark (LD) cycle, and the heart beat rate was measured both in vivo and in vitro from
3 days post‐fertilization (dpf) to 5 dpf. Furthermore, daily changes in the expression of the
clock protein Period 3 (Per3), were also characterized. Heart beat rate rhythmicity was
observed following light entrainment, and this was found to be correlated with the timing of
Per3 expression. Furthermore, the rhythmicity of the larval heart beat rate following injury
was also investigated. Together, the data collected demonstrate that the circadian clock plays
a role in regulating the function of the larval zebrafish heart, and it has a clear impact on daily
changes in the heart beat rate.
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