Chronic Exercise Accelerates Disease Progression in a Rat Model of Desminopathy
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Updated: Nov 7, 2026
Application of Chronic Stimulation to Study Contractile Activity-induced Rat Skeletal Muscle Phenotypic Adaptations
Published on: January 25, 2018
Henning T Langer1,2, Natalie Haritonow1, Aniket S Joshi1
1Department of Geriatrics and Medical Gerontology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, and Humboldt-Universität Zu Berlin, Berlin, Germany.
Background:
Desminopathy is a progressive myopathy and the most common intermediate filament disease in humans. Desmin is an essential part of the filamentous network that aligns myofibrils, anchors nuclei and mitochondria and connects the z discs to the sarcolemma. We challenged a rat model with a mutation in R349P Des, analogous to the most frequent R350P DES missense mutation in humans, through eccentric-biassed exercise training.
Methods:
R349P Des rats (Des) and their wild type (WT) and heterozygous (HET) littermates were subjected to 4 weeks of downhill running. At the end of 4 weeks, muscles were collected and assessed histologically and biochemically.
Results:
Des rats demonstrated significantly lower running capacity compared to wild type and heterozygous littermates (p < 0.0001), which exacerbated over the course of the study (p < 0.001). Running performance in Des rats decreased by ~50% after 4 weeks of downhill running. Desmin-positive skeletal muscle aggregates, a histopathological hallmark of desminopathy, were ~2-fold higher after downhill running in the Des group (p < 0.05). On a protein level, we found a differential exercise response of Des compared to WT affecting various cellular pathways concerning autophagy, proteasomal activity, energy metabolism and cytoskeletal proteins.
Conclusions:
Our results suggest an impaired ability of Des muscle to adapt to chronic eccentric-biassed exercise and a subsequent exacerbation of the functional and histopathological phenotype.
