Rapsyn Homolog RPY-1 Modulates Dose-Dependent Locomotor Responses of <em>Caenorhabditis elegan</em>s to Radial Extracorporeal Shock Waves

Background/Objectives: Radial extracorporeal shock wave therapy (rESWT) is used to treat neuromuscular disorders such as spasticity, but the mechanisms by which rESWT modulates muscle tone remain incompletely understood. One proposed mechanism involves mechanical perturbation of the neuromuscular junction (NMJ), particularly destabilization of acetylcholine receptor clusters in the postsynaptic membrane. Because rapsyn knockout mice are not viable, Caenorhabditis elegans (C. elegans) provides an alternative model through its rapsyn homolog RPY-1. This study examined whether loss of RPY-1 alters locomotor responses of C. elegans to radial extracorporeal shock wave (rESW) exposure. Methods: Wild-type worms and rpy-1 knockout worms (rpy-1-KOs) were exposed to defined numbers of rESWs. Locomotor behavior was quantified using automated tracking of parameters describing speed, trajectory and body-wave dynamics. Results: rESW exposure produced pronounced alterations in locomotor behavior across all parameters analyzed. After normalization to genotype-specific baseline values (because baseline locomotion differed between genotypes), wild-type worms and rpy-1-KOs responded similarly to moderate exposure levels. In contrast, higher exposure levels produced stronger locomotor impairment in rpy-1-KOs than in wild-type worms. Locomotor impairment was most pronounced immediately after exposure but improved during the subsequent recovery period of three hours. Conclusions: rESWs induced strong but largely reversible locomotor alterations in C. elegans during the first hours after exposure. The stronger impairment observed in rpy-1-KOs at higher exposure levels suggests that absence of the rapsyn homolog increased the vulnerability of the neuromuscular system of C. elegans to stronger mechanical perturbation induced by rESWs.