A crosstalk between the dystrophic muscle and the spinal cord neuronal populations in an aged mouse model of DMD

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive disorder caused by out-of-frame mutations in the dystrophin gene, which result in insufficient production of dystrophin protein. It is one of the most severe forms of muscular dystrophy, characterized by progressive muscle weakening and rapid loss of mobility. The primary causes of death in patients are cardiac and respiratory complications. While there is no definitive cure, corticosteroids are commonly used to reduce muscle inflammation. In recent years, biotechnological therapies aimed at restoring the reading frame of the dystrophin transcript and enabling partial production of the protein have been developed. At the cellular level, DMD is marked by severe damage and loss of skeletal myofibers due to oxidative stress, calcium imbalance, and sarcolemma instability. Chronic inflammation and the deterioration of the neuromuscular junction further exacerbate the clinical symptoms. The involvement of the neuromuscular junction and the critical role of certain dystrophin isoforms in the central nervous system necessitate a comprehensive study of the molecular mechanisms of DMD from a neuronal perspective. This thesis aims to evaluate phenotypic changes in the spinal cord of a murine model of DMD, specifically comparing male mdx -/y mice with age- and sex-matched wild-type controls. Our dual approach involves both behavioral observations and cellular morphology analysis using immunostaining techniques. We focused on examining the size, morphology, and density of various cellular subtypes in the spinal cord (primarily interneurons and motor neurons) and the dorsal root ganglia at cervical and lumbar levels. In particular, we will discuss the potential role of altered inhibitory functions of interneurons on other cell populations, such as motor neurons. ​