Glycine receptor subunit-β -deficiency in a mouse model of spasticity results in attenuated physical performance, growth and muscle strength
2020
Spasticity is the most common neurological disorder associated with increased muscle contraction causing impaired movement and gait. The aim of this study was to characterize physical performance and skeletal muscle function and phenotype of mice with a hereditary spastic mutation (B6.Cg-Glrbspa/J). Physical activity, morphological, histological and mechanical characteristics of soleus (SO) and gastrocnemius medialis (GM) muscles of juvenile and adult spastic mice were compared with their wild-type (WT) littermates. Spastic mice showed attenuated growth, and low physical activity. Gait of spastic mice was characterized by a typical hopping pattern. Spastic mice showed lower muscle forces, which were related to the smaller physiological cross-sectional area of spastic muscles. The muscle-tendon complex length-force relationship of adult GM was shifted towards shorter lengths, which was explained by attenuated longitudinal tibia growth. Spastic GM was more fatigue resistant than WT GM. This was largely explained by a higher mitochondrial content in muscle fibers and relatively higher percentage of slow type muscle fibers. Muscles of juvenile spastic mice showed similar differences compared to WT juvenile mice, but these were less pronounced than between adult mice. This study shows that in spastic mice, disturbed motor function is likely the result hyperactivity of skeletal muscle and impaired skeletal muscle growth, which progress with age.
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