Spermidine improves fast-twitch muscle histopathology and specific-force, with no impact on bone, in the <em>mdx</em> mouse model of Duchenne muscular dystrophy — ASN Events
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  3. Spermidine improves fast-twitch muscle histopathology and specific-force, with no impact on bone, in the mdx mouse model of Duchenne muscular dystrophy

Spermidine improves fast-twitch muscle histopathology and specific-force, with no impact on bone, in the mdx mouse model of Duchenne muscular dystrophy (#105)

Ahmed Al Saedi 1 2 , Nicholas Giourmas 3 , Lauryn Schaddee Van Dooren 3 , Damian Mayers 1 , Ali Ghasem-Zadeh 4 , Alan Hayes 1 2 3 , Craig Goodman 2 3 5
  1. Department of Medicine – Western Health, The University of Melbourne, St Albans, VIC, Australia
  2. Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St Albans, VIC, Australia
  3. Institute for Health and Sport, Victoria University, Melbourne , VIC, Australia
  4. Departments of Medicine and Endocrinology Austin Health, THE UNIVERSITY OF MELBOURNE, Heidelberg West, VIC, Australia
  5. Department of Anatomy and Physiology, School of Biomedical Sciences, The University of Melbourne, Parkville, Victoria, Australia

Introduction: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive skeletal and cardiac muscle degeneration, accompanied by compromised bone quality and microarchitecture. Emerging evidence from both human and mdx mouse models indicates that impaired autophagy contributes to DMD pathology. Spermidine, a naturally occurring polyamine, has been shown to stimulate autophagy, potentially via upregulation of the microtubule-associated protein MAP1S, and has demonstrated therapeutic benefits in other myopathies. This study aimed to investigate whether spermidine supplementation could improve muscle pathology and function in mdx mice, and whether these effects are associated with enhanced autophagy and MAP1S expression, while also assessing its impact on bone quality.

Methods: Three-week-old wild type (WT) and mdx mice were supplemented with 3 mM spermidine in drinking water for 13 weeks. Muscle function and histopathology were assessed in both slow-twitch (soleus) and fast-twitch (extensor digitorum longus, EDL) muscles. Markers of autophagy and MAP1S protein expression were evaluated. Bone microstructure and mechanical properties were analysed using synchrotron-generated X-ray imaging and three-point bending tests.

Results: Spermidine supplementation did not affect histopathology or contractile function in the slow-twitch soleus muscle of mdx mice. However, in fast-twitch EDL muscle, spermidine significantly improved muscle mass and specific tetanic force, accompanied by reduced centrally located nuclei and tissue infiltration. While spermidine increased MAP1S protein expression, no significant changes were observed in markers of autophagy or autophagic flux. Additionally, spermidine had no measurable effects on bone microstructure or mechanical properties in either WT or mdx mice.

Conclusion: Spermidine supplementation selectively improves fast-twitch muscle function in the mdx model of DMD, independent of detectable changes in autophagy pathways, despite increased MAP1S expression. These findings suggest a potential therapeutic role for spermidine in DMD, although the underlying mechanisms require further investigation. Notably, spermidine did not influence bone outcomes, indicating tissue-specific effects.