High-intensity interval training stimulates remyelination via the Wnt/β-catenin pathway in cuprizone-induced demyelination mouse model

ABSTRACT

Objectives

This study aims to investigate the role of high-intensity interval training (HIIT) in promoting myelin sheath recovery during the remyelination phase in cuprizone (CPZ)-induced demyelination mice and elucidate the mechanisms involving the Wnt/β-catenin pathway.

Methods

After 5 weeks of a 0.2% CPZ diet to induce demyelination, a 4-week recovery phase with a normal diet was followed by HIIT intervention. Mice body weight was monitored. Morris water maze (MWM) gauged spatial cognition and memory, while the open field test (OFT) assessed anxiety levels. Luxol fast blue (LFB) staining measured demyelination, and immunofluorescence examined myelin basic protein (MBP) and platelet-derived growth factor receptor-alpha (PDGFR-α). Western blotting analyzed protein expression, including MBP, PDGFR-α, glycogen synthase kinase-3β (GSK3β), β-catenin, and p-β-catenin. Real-time PCR detected mRNA expression levels of CGT and CST.

Results

HIIT promoted remyelination in demyelinating mice, enhancing spatial cognition, memory, and reducing anxiety. LFB staining indicated decreased demyelination in HIIT-treated mice. Immunofluorescence demonstrated increased MBP fluorescence intensity and PDGFR-α⁺ cell numbers with HIIT. Western blotting revealed HIIT reduced β-catenin levels while increasing p-β-catenin and GSK3β levels. Real-time PCR demonstrated that HIIT promoted the generation of new myelin sheaths. Additionally, the Wnt/β-catenin pathway agonist, SKL2001, decreased MBP expression but increased PDGFR-α expression.

Discussion

HIIT promotes remyelination by inhibiting the Wnt/β-catenin pathway and is a promising rehabilitation training for demyelinating diseases. It provides a new theoretical basis for clinical rehabilitation and care programs.

KEYWORDS:

• High-intensity interval training
• demyelination
• oligodendrocyte precursor cells
• cuprizone
• Wnt/β-catenin

Acknowledgments

Parts of the figure were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/). The authors would like to thank this website for its image resources. The experiments in this article were partly completed in public Experimental research center of Xuzhou Medical University.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Fei Chen: Data curation, Funding acquisition, Investigation, Writing – original draft; Bing Cheng: Data curation, Formal analysis, Investigation, Methodology; Xinqi Xu: Data curation, Funding acquisition, Investigation; Weixing Yan: Project administration, Data curation; Qiqi Meng: Investigation, Methodology; Jinfeng Liu: Funding acquisition, Resources, Data curation; Ruiqin Yao: Investigation, Data curation; Fuxing Dong: Project administration, Data curation; Yaping Liu: Project administration, Writing – review & editing. All authors have read and approved the manuscript.

Data availability statement

Data will be made available on request.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/01616412.2024.2376310.

Additional information

Funding

This study was funded by the Jiangsu Training Program of Innovation and Entrepreneurship for Undergraduates (202210313088Y).