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Multi-scale microscopic Characterization of Skeletal Muscle Fibers in an ALS Mouse Model SOD1-G93A
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International audience. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to severe muscle atrophy and functional impairment. ALS has an incidence of approximately 1 to 2 cases per 100,000 individuals per year, with most cases being sporadic (90–95%) and a smaller percentage linked to genetic mutations, including SOD1. The disease predominantly affects individuals between the ages of 50 and 70, progressing rapidly with a median survival of 2 to 5 years post-diagnosis. Despite extensive research on motor neuron degeneration, the impact of ALS on skeletal muscle at the microscopic scale remains insufficiently explored.This study aimed to characterize structural alterations in skeletal muscle fibers of an ALS mouse model (SOD1-G93A) using second harmonic generation (SHG) multiphoton microscopy and atomic force microscopy (AFM). SHG imaging was employed to assess sarcomere periodicity and orientation. In particular, the latter parameter was analyzed using the CAS3D technique, revealing significant differences between WT and SOD1-G93A mice. AFM provided morphological insights into sarcomere organization by analyzing the length of the A and I band within gastrocnemius muscle sarcomeres. The results demonstrated significant differences between ALS-affected and control fibers:for the A band, a mean length value of 1.514 µm for the WT and 1.216 µm for the SOD1-G93A were measured, while for the I band, we calculated a mean length value of 0.5652 µm for the WT and 0.4970 µm for the SOD1-G93A (N = 3, n = 76). These nanoscale disruptions further underline the structural impairment in pathological skeletal muscle. Overall, SHG analysis demonstrated a significant reduction in sarcomere periodicity in SOD1-G93A mice compared to WT controls, indicating structural dysregulation at the sarcomeric level. AFM analysis demonstrated nanoscale alterations in sarcomeric bands. These findings highlight significant structural and mechanical modifications in ALS-affected skeletal muscle, contributing to a deeper understanding of ALS muscle pathology. This work underscores the potential for novel diagnostic and therapeutic approaches targeting muscle integrity in neurodegenerative diseases.
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