Rapsyn Homolog RPY-1 Modulates Locomotor Responses of Caenorhabditis elegans 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 (AChR) clusters in the postsynaptic membrane. Because rapsyn knockout mice are not viable, Caenorhabditis elegans (C. elegans) provides an alternative model for studying neuromuscular signaling, expressing the rapsyn homolog RPY-1, a postsynaptic scaffolding protein involved in AChR organization at the NMJ. 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. Behavioral responses were analyzed both as absolute values and relative to genotype-specific baseline values. Results: rESW exposure produced pronounced alterations in locomotor behavior across all parameters analyzed. Absolute values revealed baseline differences between genotypes. After normalization to genotype-specific baseline values, wild-type worms and rpy-1-KOs responded similarly to moderate exposure levels. At higher exposure levels, genotype-dependent differences became more apparent. 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. Loss of the rapsyn homolog RPY-1 modified these responses, particularly at higher exposure levels. These findings indicate that RPY-1 influences behavioral responses to rESW exposure, while direct effects on NMJ structure or AChR organization cannot be determined from the present data.