Abstract

Nerve crush injury at focal sites causes rapid muscle atrophy in the connected muscle downstream of the affected motor end plate, and results in profound functional and metabolic deficits. This report characterizes the resultant functional and molecular changes at the post-synapse in an androgen depleted mouse model of reversible nerve injury. Weekly functional phenotyping utilizing Paw Grip Endurance Analysis (PaGE) revealed a significant functional deficit as a result of nerve crush (vs. sham procedure animals). Molecular characterization of the post-synapse after injury (gastrocnemius skeletal muscle) revealed down regulation of key neuromuscular junction genes such as MuSK and Rapsyn. While treatment with Testosterone Propionate (TP) yielded little benefit, this report highlights a Selective Androgen Receptor Modulator (SARM) that accelerates the recovery as evidenced by improved PaGE endpoints. Treatment with the SARM increased the expression of MuSK and AChR-gamma, along with augmented NMJ innervation. Collectively, this report identifies molecular events associated with nerve injury and repair and provides preliminary evidence for the therapeutic use of novel SARMs in such conditions that are associated with nerve injury.

Authors and Affiliations