5 Hz of repetitive transcranial magnetic stimulation improves cognition and induces modifications in hippocampal neurogenesis in adult female Swiss Webster mice

Adult hippocampal neurogenesis is regulated by several stimuli to promote the creation of a reserve that may facilitate coping with environmental challenges. In this regard, repetitive transcranial magnetic stimulation (rTMS), a neuromodulation therapy, came to our attention because in clinical studies it reverts behavioral and cognitive alterations related to changes in brain plasticity. Some preclinical studies emphasize the need to understand the underlying mechanism of rTMS to induce behavioral modifications. In this study, we investigated the effects of rTMS on cognition, neurogenic-associated modifications, and neuronal activation in the hippocampus of female Swiss Webster mice. We applied 5 Hz of rTMS twice a day for 14 days. Three days later, mice were exposed to the behavioral battery. Then, brains were collected and immunostained for Ki67-positive cells, doublecortin-positive (DCX+)-cells, calbindin, c-Fos and FosB/Delta-FosB in the dentate gyrus. Also, we analyzed mossy fibers and CA3 with calbindin immunostaining. Mice exposed to rTMS exhibited cognitive improvement, an increased number of proliferative cells, DCX cells, DCX cells with complex dendrite morphology, c-Fos and immunoreactivity of FosB/Delta-FosB in the granular cell layer. The volume of the granular cell layer, mossy fibers and CA3 in rTMS mice also increased. Interestingly, cognitive improvement correlated with DCX cells with complex dendrite morphology. Also, those DCX cells and calbindin immunoreactivity correlated with c-Fos in the granular cell layer. Our results suggest that 5 Hz of rTMS applied twice a day modify cell proliferation, doublecortin cells, mossy fibers and enhance cognitive behavior in healthy female Swiss Webster mice.