Restoration of DNA Integrity and Cell Cycle by Electric Stimulation in Planarian Tissues Damaged by Ionizing Radiation

Exposure to high levels of ionizing γ-radiation leads to irreversible DNA damage and cell death. Here, we establish that exogenous application of electric stimulation enables cellular plasticity to reestablish stem cell activity in tissues damaged by ionizing radiation. We show that sub-threshold direct current stimulation (DCS) rapidly restores pluripotent stem cell populations previously eliminated by lethally γ-irradiated tissues of the planarian flatworm Schmidtea mediterranea . Our findings reveal that DCS enhances DNA repair, transcriptional activity, and cell cycle entry in post-mitotic cells. These responses involve rapid increases in cytosolic [Ca 2+ ] through the activation of L-type Cav channels and intracellular Ca 2+ stores leading to the activation of immediate early genes and ectopic expression of stem cell markers in postmitotic cells. Overall, we show the potential of electric current stimulation to reverse damaging effects of high dose γ-radiation in adult tissues. Furthermore, our results provide mechanistic insights describing how electric stimulation effectively translates into molecular responses capable of regulating fundamental cellular functions without the need for genetic or pharmacological intervention.