Assessment of the Effect of Valproic Acid on Regeneration in Eisenia fetida

Earthworms are unique and valuable model to study regeneration. The regeneration process in annelids is similar to that of vertebrates. Therefore, annelids are suitable experimental models for exploring ways to regulate the regeneration ability. In this study, we studied segmental regeneration in the earthworm Eisenia fetida by amputating the animal at its 40th segment. Valproic Acid (VPA), a known HDAC (Histone deacetylase) inhibitor was applied at the site of amputation to assess its effect on regeneration process. The rate of regeneration was studied in control and VPA treated earthworms. Subsequently, the healing of severed ventral nerve cord was also studied by Rapid Escape Response (RER) Assay. Furthermore, we used computational approach to study the VPA-protein interactome using STITCH tool to predict the molecular mechanism of action of this molecule. Our results revealed that VPA significantly reduced the rate of segmental regeneration but promoted ventral nerve cord healing as exhibited by RER assay. Our in silico data of VPA-protein interactome indicated the enrichment of GO pathways related to neuronal regeneration. Altogether, our findings suggest the potential clinical applications of VPA for the treatment of peripheral nerve injury.