Establish a non‐invasive mouse model and analyze RNA profile to observe the exercise effects on disuse‐induced muscle atrophy

Yu-Jung Cheng, Tetsuya Takahashi
Purpose:

This study aims to investigate the mechanisms by which exercise mitigates muscle atrophy using a non-invasive mouse model, integrating findings from new RNA-seq data with previous research.

Methods:

The non-invasive model utilized thermoplastic materials to immobilize the hind limbs of mice for seven days without surgical intervention. Two forms of exercise were administered as therapeutic interventions: resistance and swimming. For the resistance exercise group, mice underwent daily weight-bearing training with loads increasing from 80% to 100% of their body weight. Each session involved climbing a mesh for five minutes. The swimming group participated in daily swimming sessions, starting at 15 minutes and extending to 30 minutes by the end of the week. After seven days, muscle tissues from both exercised and control groups were harvested, including the gastrocnemius and tibialis anterior muscles from both immobilized and non-immobilized limbs. The collected tissues were weighed and either prepared for histological staining or subjected to NGS-RNA seq analysis to assess transcriptomic changes induced by exercise in atrophic muscles.

Results:

The study confirmed that both resistance and swimming exercises significantly improved muscle atrophy as evidenced by increased muscle mass. Histological analyses showed resistance exercise can increase muscle fiber cross-sectional area, which reduced in immobilization group. Through RNA-seq analysis, we found resistance training specifically decreased the expression of inflammatory markers such as CCL6 and CCR5, which was consistent with findings from the previously published article. Furthermore, exercise not only affects muscle protein synthesis pathways but also modulates inflammatory and immune response pathways, enhancing muscle recovery and function. 

Conclusion(s):

This study not only confirms that resistance exercise can effectively counteract disuse-induced muscle atrophy through anti-inflammatory pathways, but also highlights the utility of the newly established non-invasive mouse model and comprehensive RNA-seq analysis. These innovative approaches provide a deeper understanding of the molecular mechanisms underlying exercise benefits, paving the way for targeted therapies in muscle atrophy treatment.

Implications:

This project emphasizes the significance of applying animal model and RNA-seq analysis to understand the therapeutic benefits of exercise on disuse muscle atrophy. The findings provide evidence-based support for incorporating specific exercise regimens into physiotherapy practices. By understanding the molecular basis of how resistance and endurance training counteract muscle wasting, the results would empower future physiotherapists with the knowledge to implement effective, personalized exercise interventions on patients with disuse muscle atrophy. 




Funding acknowledgements:
This study was supported by the Taiwanese Ministry of Science and Technology (Grant Number: NSTC 113-2410-H-039-011 - and NSTC 112-2410-H-039-008 -).
Keywords:
muscle atrophy
resistance exercise
next-generation RNA sequencing
Primary topic:
Basic science including molecular and cellular health
Second topic:
Innovative technology: information management, big data and artificial intelligence
Third topic:
Research methodology, knowledge translation and implementation science
Did this work require ethics approval?:
Yes
Name the institution and ethics committee that approved your work:
Affidavit of Approval of Animal Use Protocol China Medical University
Provide the ethics approval number:
CMUIACUC-2024-065
Has any of this material been/due to be published or presented at another national or international conference prior to the World Physiotherapy Congress 2025?:
No

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