Repetitive Transcranial Magnetic Stimulation Improves Depression-like Behavior in Rats by Promoting Neural Stem Cell Proliferation and Differentiation

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is a novel non-invasive neuromodulation technique with neuroprotective properties and is used to treat depression. However, the underlying mechanism of action remains unclear. In this study, we examined the possible mechanism mediating the antidepressant effect of rTMS using animal experiments. Specific pathogen-free rats were treated with rTMS after exposure to social isolation combined with chronic unpredictable mild stress (CUMS). After four weeks of CUMS, the rats exhibited a significant decrease in spatial working memory assessed using open-field testing, a general loss of interest assessed with the sucrose preference test, and a significant reduction in spatial recognition memory ability assessed using the Y-maze. These behavioral deficits were accompanied by decreased numbers of astrocytes in the hippocampus, decreased expression of glial fibrillary acidic protein (GFAP), increased numbers of neural stem cells (NSCs), and increased expression of nestin protein. These results indicated that neuron damage occurred in the depression-like rats. After rTMS intervention, the depression-like behavior was alleviated significantly, and the numbers of NSCs and astrocytes, as well as the expression of GFAP and nestin proteins, returned to normal levels. Overall, it is likely that attenuation of NSC proliferation and differentiation into astrocytes produced a neuroprotective effect on hippocampal neurons, which might partly explain the mechanism by which rTMS alleviates depression.