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

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.