Direct current stimulation (DCS) modulates gene expression related to human diseases in the marine chordate Botryllus schlosseri

Objective: Direct current stimulation (DCS) -i.e., the application of a static electric field to the brain through surface scalp electrodes- emerged as a novel therapy for neuropsychiatric disorders. In this study, DCS-induced changes in gene expression were assessed on Botryllus schlosseri, a ubiquitous simple colonial chordate living in temperate seas and sharing genetic remarkable similarities with mammals. Methods: Colonies underwent either sham or real DCS stimulation. Behavioral assessments, including the Siphon Stimulation Test and heart-rate measurements, were conducted before and at three intervals post-stimulation (3, 24, and 48 h). Gene expression was analyzed with sequencing reads via Trimmomatic®. Results: Analysis of heart rate frequency revealed post-treatment differences between the groups immediately after stimulation (p = 0.001), with the effect decreasing over time. Real DCS differentially expressed 164 genes at three h post-DCS, 123 at 24 h, and 199 at 48 h. Conclusions: Our study introduces a novel pre-clinical model for DCS application demonstrating for the first in vivo time an after-effect on gene expression related to inflammation, human development, and neurodegeneration. To the best of our knowledge, this is the first paper addressing DCS effects on gene expression in a living animal model.