rTMS ameliorated depressive-like behaviors by restoring HPA axis balance and prohibiting hippocampal neuron apoptosis in a rat model of depression

•CUMS rats were observed a significant decrease in body weight, the sucrose consumption and the horizontal/vertical distance in the OFT, as well as disorder of cell morphology were also observed in the hippocampal neurons.•CUMS rats showed Bax protein expression levels increased in the hippocampus and ACTH and CORT expression levels increased in plasma.•rTMS treatment down-regulated Bax protein expression levels and ACTH and CORT expression levels, improved cell morphology and ameliorated depressive-like behaviors.•rTMS could protect against CUMS-induced changes through reducing Bax production and restoring the balance of the HPA axis. Repetitive transcranial magnetic stimulation (rTMS) has been widely used to treat depression. The mechanistic basis for the effects of rTMS is not well understood, although previous studies have suggested that it involves the regulation of hypothalamic-pituitary-adrenocortical (HPA) axis and protection of hippocampal neurons. We investigated this in the present study using a chronic unpredictable mild stress (CUMS) paradigm in Sprague-Dawley rats. The rats were subjected to rTMS for 15 consecutive days, and body weight, sucrose consumption, and locomotor activity were evaluated. B cell lymphoma-2-associated X protein (Bax) expression was assessed by immunohistochemistry; cell morphology was examined by Nissl staining; and adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels in the hippocampus were measured by enzyme-linked immunosorbent assay. CUMS decreased body weight and sucrose consumption in rats along with horizontal/vertical distance traveled in the open field test. Rats subjected to CUMS also showed increased levels of Bax as well as ACTH and CORT; the hippocampal neurons in these animals had abnormal morphology and were reduced in number. rTMS reversed these changes and improved depression-like behaviors. Thus, rTMS abrogates the loss of hippocampal neurons and restores the balance of the HPA axis in the treatment of depression.