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The evaluation of zebrafish cardiovascular and behavioral functions through microfluidics.

ABSTRACT: This study proposed a new experimental approach for the vascular and phenotype evaluation of the non-anesthetized zebrafish with representative imaging orientations for heart, pectoral fin beating, and vasculature views by means of the designed microfluidic device through inducing the optomotor response and hydrodynamic pressure control. In order to provide the visual cues for better positioning of zebrafish, computer-animated moving grids were generated by an in-house control interface which was powered by the larval optomotor response, in conjunction with the pressure suction control. The presented platform provided a comprehensive evaluation of internal circulation and the linked external behaviors of zebrafish in response to the cardiovascular parameter changes. The insights from these imaging sections was extended to identify the linkage between the cardiac parameters and behavioral endpoints. In addition, selected chemicals such as ethanol and caffeine were employed for the treatment of zebrafish. The obtained findings can be applicable for future investigation in behavioral drug screening serving as the forefront in psychopharmacological and cognition research.

SUBMITTER: Subendran S

PROVIDER: S-EPMC8257654 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Ractopamine (RAC) is a beta-adrenoceptor agonist that is used to promote lean and increased food conversion efficiency in livestock. This compound has been considered to be causing behavioral and physiological alterations in livestock like pig. Few studies have addressed the potential non-target effect of RAC in aquatic animals. In this study, we aimed to explore the potential physiological response after acute RAC exposure in zebrafish by evaluating multiple endpoints like locomotor activity, oxygen consumption, and cardiovascular performance. Zebrafish larvae were subjected to waterborne RAC exposure at 0.1, 1, 2, 4, or 8 ppm for 24 h, and the corresponding cardiovascular, respiratory, and locomotion activities were monitored and quantified. In addition, we also performed in silico molecular docking for RAC with 10 zebrafish endogenous β-adrenergic receptors to elucidate the potential acting mechanism of RAC. Results show RAC administration can significantly boost locomotor activity, cardiac performance, oxygen consumption, and blood flow rate, but without affecting the cardiac rhythm regularity in zebrafish embryos. Based on structure-based flexible molecular docking, RAC display similar binding affinity to all ten subtypes of endogenous β-adrenergic receptors, from adra1aa to adra2db, which are equivalent to the human one. This result suggests RAC might act as high potency and broad spectrum β-adrenergic receptors agonist on boosting the locomotor activity, cardiac performance, and oxygen consumption in zebrafish. To validate our results, we co-incubated a well-known β-blocker of propranolol (PROP) with RAC. PROP exposure tends to minimize the locomotor hyperactivity, high oxygen consumption, and cardiac rate in zebrafish larvae. In silico structure-based molecular simulation and binding affinity tests show PROP has an overall lower binding affinity than RAC. Taken together, our studies provide solid in vivo evidence to support that RAC plays crucial roles on modulating cardiovascular, respiratory, and locomotory physiology in zebrafish for the first time. In addition, the versatile functions of RAC as β-agonist possibly mediated via receptor competition with PROP as β-antagonist.

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The evaluation of zebrafish cardiovascular and behavioral functions through microfluidics.

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