Quantification of the influence of drugs on zebrafish larvae swimming kinematics and energetics

Abstract

The use of zebrafish larvae has aroused wide interest in the medical field for its potential role in the development of new therapies. The larvae grow extremely quickly and the embryos are nearly transparent which allows easy examination of its internal structures using fluorescent imaging techniques. Medical treatment of zebrafish larvae can directly influence its swimming behaviours. These behaviour changes are related to functional changes of central nervous system and transformations of the zebrafish body such as muscle mechanical power and force variation, which cannot be measured directly by pure experiment observation. To quantify the influence of drugs on zebrafish larvae swimming behaviours and energetics, we have developed a novel methodology to exploit intravital changes based on observed zebrafish locomotion. Specifically, by using an in-house MATLAB code to process the recorded live zebrafish swimming video, the kinematic locomotion equation of a 3D zebrafish larvae was obtained, and a customised Computational Fluid Dynamics tool was used to solve the fluid flow around the fish model which was geometrically the same as experimentally tested zebrafish. The developed methodology was firstly verified against experiment, and further applied to quantify the fish internal body force, torque and power consumption associated with a group of normal zebrafish larvae vs. those immersed in acetic acid and two neuroactive drugs. As indicated by our results, zebrafish larvae immersed in 0.01% acetic acid display approximately 30% higher hydrodynamic power and 10% higher cost of transport than control group. In addition, 500 μM diphenylhydantoin significantly decreases the locomotion activity for approximately 50% lower hydrodynamic power, whereas 100 mg/L yohimbine has not caused any significant influences on 5 dpf zebrafish larvae locomotion. The approach has potential to evaluate the influence of drugs on the aquatic animal’s behaviour changes and thus support the development of new analgesic and neuroactive drugs.

Behavioral adaptation to changing energy constraints via altered frequency of movement selection

“…Our power expenditures were in the same range as Bale et al [58], who computed 1.67 erg/s for steady swimming at approximately 1.2 cm/s, though ours are generally slightly lower, likely due to steady movement requiring more power. Zhao et al [65] developed a CFD method to achieve high-throughput simulations of larval zebrafish, however the analysis was restricted to quasi-steady high-speed cruising movements and excluded sudden starts. Li et al [66] developed a CFD method to simulate sudden-start escape bouts in larval zebrafish, however the full behavioral repertoire was not considered.…”

Standardization of zebrafish drug testing parameters for muscle diseases

“…These assays can record muscle performance over a prolonged period and overall locomotor activity in developing zebrafish larvae. The swimming behavior of wild-type or mutant zebrafish can be monitored through a visual tracking system measuring the mean distance, velocity and overall activity, thereby estimating skeletal muscle locomotor function ( Zhao et al, 2020 ). Before 6 dpf, embryos and larvae have sustained periods of inactivity, which can confound the measurement of locomotion.…”

Zebrafish as a Model for the Study of Lipid-Lowering Drug-Induced Myopathies

“…The medicament treatment can affect the zebrafish muscle mechanical power, and directly change the swimming behaviour. Changes in the zebrafish locomotion kinematics and energetics can also be analysed quantitatively, e.g., using customized software [ 169 , 170 ]. One such methodology, based on the recording of muscle contraction and mathematical algorithms, was applied to quantify the fish internal body force, torque, and power consumption in reaction to neuroactive drugs [ 170 ].…”