Changes in Physiopathological Markers in Myotonic Dystrophy Type 1 Skeletal Muscle: A 3-Year Follow-up Study

Roussel, M.-P., Ravel-Chapuis, A., Gobin, J., Jasmin, B. J., Leduc-Gaudet, J.-P., Gagnon, C. et Duchesne, E. (2024). Changes in Physiopathological Markers in Myotonic Dystrophy Type 1 Skeletal Muscle: A 3-Year Follow-up Study. Journal of Neuromuscular Diseases, 11 (5). pp. 981-995. ISSN 2214-3599 2214-3602 DOI 10.3233/JND-230139

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Résumé

Abstract

Background:
Myotonic dystrophy type 1 (DM1) is a slowly progressive disease caused by abnormal CTG repetitions on the dystrophia myotonica protein kinase (DMPK) gene. Long mRNA from CTG repetitions stabilizes in nuclear foci and sequester muscleblind-like splicing regulator 1 (MBNL1). Cardinal signs of DM1 include muscle wasting and weakness. The impacts of DM1 progression on skeletal muscle are under-researched.

Objective:
Identifying physiopathological markers related to maximal strength loss over time in DM1.

Methods:
Twenty-two individuals with DM1 participated in two maximal isometric muscle strength (MIMS) evaluations of their knee extensors and two vastus lateralis muscle biopsies, 3 years apart. Muscle fiber typing, size (including minimal Feret’s diameter [MFD] and atrophy/hypertrophy factors [AF/HF]), and nuclear foci and MBNL1 colocalization (foci/MBNL1+) were evaluated. Immunoblotting was used to measure glycogen synthase kinase-3 beta (GSK3β), p62, LC3BI, LC3BII, and oxidative phosphorylation proteins.

Results:
There are significant correlations between the fold changes of MIMS with type 1 fiber MFD (ρ= 0.483) and AF (ρ= –0.514). Regression analysis shows that baseline percentage of foci/MBNL1+ nuclei and strength training explain 44.1% of foci/MBNL1+ nuclei percentage variation over time. There are fair to excellent correlations between the fold changes of MIMS and GSK3β (ρ= 0.327), p62 (ρ= 0.473), LC3BI (ρ= 0.518), LC3BII (ρ= –0.391) and LC3BII/LC3BI (ρ= –0.773).

Conclusion:
Type 1 MFD decrease and AF increase are correlated with MIMS loss. There seems to be a plateau effect in foci/MBNL1+ nuclei accumulation and strength training helps decrease this accumulation. Autophagy marker LC3BII/LC3BI ratio has a good biomarker potential of MIMS loss, but more investigations are needed.

Type de document:	Article
Mots-clés libres:	Myotonic dystrophy type 1 Natural history study Maximal muscle strength Histomorphology Nuclear foci and MBNL1 colocalization Protein expression
Date de dépôt:	17 sept. 2025 17:36
Dernière modification:	17 sept. 2025 17:36
Version du document déposé:	Version officielle de l'éditeur
URI:	https://depot-e.uqtr.ca/id/eprint/12242

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