Abstract
Psychological stress is one of the factors associated with human cardiovascular disease. Here, we demonstrate that acute perceived stress impairs the natural capacity of heart regeneration in zebrafish. Beside physical and chemical disturbances, intermittent crowding triggered an increase in cortisol secretion and blocked the replacement of fibrotic tissue with new myocardium. Pharmacological simulation of stress by pulse treatment with dexamethasone/adrenaline reproduced the regeneration failure, while inhibition of the stress response with anxiolytic drugs partially rescued the regenerative process. Impaired heart regeneration in stressed animals was associated with a reduced cardiomyocyte proliferation and with the downregulation of several genes, including igfbp1b, a modulator of IGF signalling. Notably, daily stress induced a decrease in Igf1r phosphorylation. As cardiomyocyte proliferation was decreased in response to IGF-1 receptor inhibition, we propose that the stress-induced cardiac regenerative failure is partially caused by the attenuation of IGF signalling. These findings indicate that the natural regenerative ability of the zebrafish heart is vulnerable to the systemic paracrine stress response.
Highlights
In most living organisms, the experience of multiple environmental and physiological challenges has driven the development of a vital stress response system
As cardiomyocyte proliferation was decreased in response to insulin-like growth factors (IGF)-1 receptor inhibition, we propose that the stress-induced cardiac regenerative failure is partially caused by the attenuation of IGF signalling
We considered crowding as a suitable experimental approach to study the effect of perceived stress on heart regeneration in zebrafish
Summary
The experience of multiple environmental and physiological challenges has driven the development of a vital stress response system. When facing a life-threatening situation, animals instinctively enter in a fightor-flight mode to enhance the chances of their survival In vertebrates, this innate reaction relies on the activation of the central nervous system orchestrating rapid and powerful systems to focus the energy resources on cognitive and muscular performance. This innate reaction relies on the activation of the central nervous system orchestrating rapid and powerful systems to focus the energy resources on cognitive and muscular performance Among these networks, the hypothalamus –pituitary– adrenal (HPA) axis and the sympathetic nervous system play a crucial role by, respectively, triggering the release of corticosteroids and adrenaline/noradrenaline, which are the primary stress hormones [1,2]. The studies in fish demonstrated that cortisol and nor-/adrenaline promote multiple physiological changes, including an enhanced oxygen uptake from the gills and an increase in glucose uptake, in order to optimize task execution during environmental perturbations [3,4,5]
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