Assessment of skeletal muscle deformability during clinical paralysis in EAE, a mouse model of multiple sclerosis

Abstract

Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), are neurodegenerative diseases associated with inflammation and demyelination of the central nervous system, often leading to severe motor deficits, including progressive paralysis and spasticity. Although the neurological aspects of MS and EAE are widely described, the influence of disease progression on skeletal muscle structure and mechanics remains a largely unexplored field. In the present study, we assessed skeletal muscle deformability during EAE-induced paralysis using atomic force microscopy (AFM), histological examination, and analysis of dystrophin and laminin expression in relation to EAE disease severity. Nanomechanical measurements showed a biphasic response of forelimb muscles: an early increase in muscle rigidity at disease onset, a marked decrease at the peak of the disease, and a later increase in the chronic phase. Hindlimb muscles revealed a similar but more gradual rigidity progression. Our study revealed disease phase-dependent alterations of skeletal muscle histology, with changes in myofiber cross-sectional area, the presence of fibers with centrally located nuclei and increased collagen accumulation, particularly in the peak and chronic phases. Immunofluorescence and Western blot studies revealed decreased expression of dystrophin and laminin, particularly in the chronic phase of EAE, suggesting that cytoskeletal disorganization and extracellular matrix remodeling are contributing factors. These results demonstrate that EAE-related paralysis includes progressive biomechanical and structural changes in skeletal muscles, exacerbating motor disability. Understanding the musculoskeletal consequences of MS-like disease could provide a more comprehensive overview of disease pathology and might motivate therapeutic strategies targeting muscle integrity along with neuronal repair.