Zebrafish Model for Studying Dexamethasone-Induced Muscle Atrophy and Preventive Effect of Maca (Lepidium meyenii).

You-Jin Jeon,Jun-Geon Je,Hye-Won Yang,Bomi Ryu

doi:10.3390/cells10112879

Abstract

Loss of myofibers during muscle atrophy affects functional capacity and quality of life. Dexamethasone, an inducer of rapid atrophy of skeletal myofibers, has been studied as a glucocorticoid receptor in muscle atrophy or motor neurodegeneration. In this study, we examined dexamethasone-induced muscle atrophy using zebrafish (Danio rerio), a vertebrate model, and assessed whether administration of Lepidium meyenii (maca) as a dietary supplement can prevent muscle atrophy. Changes in skeletal myofibers in zebrafish were evaluated after exposure to dexamethasone for different periods and at different concentrations. Under optimized conditions, zebrafish pre-fed with maca for 3 days were exposed to 0.01% dexamethasone for 1 h/day for 7 days. Thereafter, myofiber loss, damaged muscle contractile proteins, and abnormal exploratory behavior due to the structural and functional impairment of skeletal muscle associated with muscle atrophy were investigated using hematoxylin–eosin, immunofluorescence staining, and behavioral analyses. Our findings suggest that dexamethasone induces muscle atrophy in zebrafish, inhibiting exploratory behavior by inducing myofiber loss, inhibiting muscle contraction, and causing changes in endurance and velocity. Thus, the zebrafish model can be used to screen pharmaceutical agents and to study muscle atrophy. Furthermore, maca is a potential dietary supplement to prevent muscle atrophy, as it protects muscle fibers.

Highlights

In the human body, skeletal muscle is essential for the homeostasis of metabolic parameters, such as basal metabolic rate, glucose uptake, and lipid utilization [1]
No studies have investigated the use of glucocorticoids to induce muscle atrophy in the zebrafish model, due to the high level of similarity between human and zebrafish glucocorticoid receptors, this animal model can be a valuable tool in research aimed at elucidating the mechanisms underlying muscle atrophy [40]
Pretreatment with maca at 1% and 3% significantly increased myofiber cross-sectional area (CSA), respectively, compared to that maca at 1% and 3% significantly increased myofiber CSA, respectively, compared to that in the dexamethasone/saline group (#### p < 0.0001). These results showed that maca prein the dexamethasone/saline group (#### p < 0.0001). These results showed that maca treatment exerted a protective effect against dexamethasone-induced muscle atrophy in pretreatment exerted a protective effect against dexamethasone-induced muscle atrophy in zebrafish, protecting myofibers by preventing the reduction in myofiber size

Summary

Introduction

Skeletal muscle is essential for the homeostasis of metabolic parameters, such as basal metabolic rate, glucose uptake, and lipid utilization [1]. The balance of homeostasis between protein synthesis and degradation maintains muscle mass within myofibers [2]. Abnormal regulation of such fibers can interfere with the contractile properties of myofibers, rendering them less stable and more susceptible to contraction-induced damage, which eventually leads to muscle atrophy [3]. The reduction in skeletal muscle mass and myofiber size is associated with several metabolic disorders, including pathological fractures and functional deterioration [4]. Muscle atrophy refers to the loss of skeletal muscle mass, strength, and myofiber size due to a range of physiological conditions, including denervation, immobilization, corticosteroid exposure, and aging [5]. The excessive loss of muscle mass and impairment of muscle contractile function in muscle atrophy can be indicators of negative prognosis and impaired functional efficacy [7]

Methods

Results

Conclusion