Research ReportEffects of single and repeated electroconvulsive stimulation on hippocampal cell proliferation and spontaneous behaviors in the rat

Electroconvulsive therapy (ECT) has therapeutic effects on refractory depression and schizophrenia, although its biological mechanisms are still unclear. Recent studies in rodents suggest that electroconvulsive stimulation-induced seizures (ECSs) influence hippocampal adult neurogenesis, which has gained considerable traction as a possible cellular substrate for the treatment of depression. The aim of this study is to explore alteration of neurogenesis in the hippocampus following ECSs and the relationship between neurogenesis and behavior in rats. In the present study, we administered a single or 10-repeated application of electroconvulsive stimulations that reliably resulted in seizure (an animal model of electroconvulsive therapy) to rats. Then cell proliferation of newborn cells in the subgranular zone (SGZ) of the dentate gyrus (DG) was investigated 3 and 14 days after ECS treatments. Cell differentiation was also examined 4 weeks after newly formed cells were confirmed. As a result, ECS-induced cell proliferation in the hippocampus showed biphasic changes after ECS. The amount of cell proliferation at 3 days after the last ECS increased twice as much as the sham group. However, the number of proliferating cells at 14 days later decreased to a half of the sham level. Differentiation of newly formed cells was not influenced in ECS-treated groups compared with sham-treated groups. In addition, we investigated the effects of ECS on behavioral changes in rats by measuring locomotor activity in an open field test and spontaneous alteration behavior in a Y-maze test. Spontaneous behavior and memory function were not influenced by repeated ECSs. These results suggest that repeated ECSs affect progenitors that have a limited ability for cell proliferation, like amplifying progenitors, to increase newly generated neurons without negative behavioral change.

► ECS-induced cell proliferation in the hippocampus showed biphasic changes after ECSs. ► Differentiation of newly formed cells was not influenced in ECS-treated groups. ► Learning behaviors and locomotor activities were not influenced by ECSs. ► It suggests that repeated ECSs increase newly generated neurons without negative behavioral change.