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

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 mech...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Experimental Gerontology
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Online Access:http://www.sciencedirect.com/science/article/pii/S0531556524002614
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author 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
author_facet 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
author_sort Chen-Chen Sun
collection DOAJ
description 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.
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spelling doaj-art-10b73c6b7f1a4250bf4b96f5088b945f2025-08-20T02:10:50ZengElsevierExperimental Gerontology1873-68152024-12-0119811261510.1016/j.exger.2024.112615Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanismsChen-Chen Sun0Ye-Jun Li1Dan-Ting Zhu2Zhang-Lin Chen3Jiang-Ling Xiao4Xiang-Tao Chen5Lan Zheng6Xi-Yang Peng7Chang-Fa Tang8Institute 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, ChinaSchool of Educational Science, Hunan Normal University, Changsha, Hunan 410012, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey 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.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.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.http://www.sciencedirect.com/science/article/pii/S0531556524002614Skeletal muscle atrophyZebrafishDexamethasoneMitochondrial dysfunctionEndoplasmic reticulum stress
spellingShingle 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
Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms
Experimental Gerontology
Skeletal muscle atrophy
Zebrafish
Dexamethasone
Mitochondrial dysfunction
Endoplasmic reticulum stress
title Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms
title_full Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms
title_fullStr Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms
title_full_unstemmed Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms
title_short Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms
title_sort establishment of a dexamethasone induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms
topic Skeletal muscle atrophy
Zebrafish
Dexamethasone
Mitochondrial dysfunction
Endoplasmic reticulum stress
url http://www.sciencedirect.com/science/article/pii/S0531556524002614
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