Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms

Chen-Chen Sun; Ye-Jun Li; Dan-Ting Zhu; Zhang-Lin Chen; Jiang-Ling Xiao; Xiang-Tao Chen; Lan Zheng; Xi-Yang Peng; Chang-Fa Tang

Experimental Gerontology (Dec 2024)

Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms

Chen-Chen Sun,
Ye-Jun Li,
Dan-Ting Zhu,
Zhang-Lin Chen,
Jiang-Ling Xiao,
Xiang-Tao Chen,
Lan Zheng,
Xi-Yang Peng,
Chang-Fa Tang

Affiliations

Chen-Chen Sun: Institute of Physical Education, Hunan First Normal University, Changsha, Hunan 410205, China; Key Laboratory of Physical Fitness and Exercise Rehabilitation, State Key Laboratory of Developmental Biology of Freshwater Fish of the Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, China
Ye-Jun Li: School of Educational Science, Hunan Normal University, Changsha, Hunan 410012, China
Dan-Ting Zhu: Key Laboratory of Physical Fitness and Exercise Rehabilitation, State Key Laboratory of Developmental Biology of Freshwater Fish of the Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, China
Zhang-Lin Chen: Key Laboratory of Physical Fitness and Exercise Rehabilitation, State Key Laboratory of Developmental Biology of Freshwater Fish of the Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, China
Jiang-Ling Xiao: Key Laboratory of Physical Fitness and Exercise Rehabilitation, State Key Laboratory of Developmental Biology of Freshwater Fish of the Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, China
Xiang-Tao Chen: Key Laboratory of Physical Fitness and Exercise Rehabilitation, State Key Laboratory of Developmental Biology of Freshwater Fish of the Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, China
Lan Zheng: Key Laboratory of Physical Fitness and Exercise Rehabilitation, State Key Laboratory of Developmental Biology of Freshwater Fish of the Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, China
Xi-Yang Peng: Key Laboratory of Physical Fitness and Exercise Rehabilitation, State Key Laboratory of Developmental Biology of Freshwater Fish of the Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, China; Corresponding authors at: Key Laboratory of Physical Fitness and Exercise Rehabilitation of the Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, China.
Chang-Fa Tang: Key Laboratory of Physical Fitness and Exercise Rehabilitation, State Key Laboratory of Developmental Biology of Freshwater Fish of the Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, China; Corresponding authors at: Key Laboratory of Physical Fitness and Exercise Rehabilitation of the Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, China.

Journal volume & issue: Vol. 198
p. 112615

Abstract

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Background: Skeletal muscle atrophy is one of the main side effects of high-dose or continuous use of glucocorticoids (such as dexamethasone). However, there are limited studies on dexamethasone-induced skeletal muscle atrophy in zebrafish and even fewer explorations of the underlying molecular mechanisms. This study aimed to construct a model of dexamethasone-induced skeletal muscle atrophy in zebrafish and to investigate the molecular mechanisms. Methods: Zebrafish soaked in 0.01 % dexamethasone solution for 10 days. Loli Track (Denmark) and Loligo Swimming Respirometer were used to observe the effect of dexamethasone on swimming ability. The effects of dexamethasone on zebrafish skeletal muscle were observed by Transmission electron microscopy, H&E, and wheat germ agglutinin techniques. Enriched genes and signaling pathways were analyzed using Transcriptome sequencing. Further, the levels of mitochondrial and endoplasmic reticulum-related proteins were examined to investigate possible mechanisms. Results: 0.01 % dexamethasone reduced zebrafish skeletal muscle mass (p < 0.05), myofibre size and cross-sectional area (p < 0.001), and increased protein degradation (ubiquitination and autophagy) (p < 0.05). In addition, 0.01 % dexamethasone reduced the swimming ability of zebrafish, as evidenced by the reluctance to move, fewer movement trajectories, decreased total distance traveled (p < 0.001), average velocity of movement (p < 0.001), oxygen consumption (p < 0.001), critical swimming speed (p < 0.01) and increased exhaustive swimming time (p < 0.001). Further, 0.01 % dexamethasone-induced mitochondrial dysfunction (decreased mitochondrial biogenesis, disturbs kinetic homeostasis, increased autophagy) and endoplasmic reticulum stress. Conclusions: 0.01 % dexamethasone induces skeletal muscle atrophy and impairs the swimming ability of zebrafish through mitochondrial dysfunction and endoplasmic reticulum stress.

Published in Experimental Gerontology

ISSN: 1873-6815 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine; Science: Biology (General)
Website: https://www.sciencedirect.com/journal/experimental-gerontology

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