High-frequency repetitive transcranial magnetic stimulation mitigates depression-like behaviors in CUMS-induced rats via FGF2/FGFR1/p-ERK signaling pathway

Abstract

High-frequency repetitive transcranial magnetic stimulation (rTMS) is a widely used and effective biological treatment for depression. Although previous studies have shown that astrocyte function may be modified by rTMS, the specific neurobiological mechanisms underlying its antidepressant action are not clear. Substantial evidence has accumulated indicating that neurotrophin dysfunction and neuronal apoptosis play a role in the development of depression. To evaluate this hypothesis, we applied a chronical unpredictable mild stress (CUMS) protocol to induce depression-like behaviors in rats, followed by the delivery of 10-Hz rTMS for 3 weeks. Behavioral outcome measures consisted of a sucrose preference test, forced swimming test, and open field test. Histological analysis focused on apoptosis, expression of GFAP and FGF2, and FGF2 pathway-related proteins. The results showed that after rTMS treatment, the rats’ sucrose preference increased, open field performance improved while the immobility time of forced swimming decreased. The behavioral changes seen in rTMS treated rats were accompanied by marked reductions in the number of TUNEL-positive neural cells and the level of expression of BAX and by an increase in Bcl2. Furthermore, the expression of GFAP and FGF2 was increased, along with activation of FGF2 downstream pathway. These results suggest that rTMS treatment can improve depression-like behavior, attenuate neural apoptosis, and reverse reduction of astrocytes in a rat model of depression. We hypothesize that the therapeutic action of rTMS in CUMS-induced rats is linked to the activation of the FGF2/FGFR1/p-ERK signaling pathway.