The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China; Henan Engineering Research Center of Physical Diagnostics and Treatment Technology for the Mental and Neurological Diseases, Xinxiang, Henan 453002, China.
The First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Neurorestoratology, Weihui, Henan 453100, China; The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China.
Brain Res Bull. 2022 Jun 1;183:94-103. doi: 10.1016/j.brainresbull.2022.02.020. Epub 2022 Mar 2.
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.
高频重复经颅磁刺激（rTMS）是一种广泛应用且有效的治疗抑郁症的生物学方法。虽然先前的研究表明，星形胶质细胞的功能可能会受到 rTMS 的改变，但 rTMS 抗抑郁作用的确切神经生物学机制尚不清楚。大量证据表明，神经营养因子功能障碍和神经元凋亡在抑郁症的发展中起作用。为了评估这一假设，我们应用慢性不可预测性轻度应激（CUMS）方案在大鼠中诱导出类似抑郁的行为，然后进行 10-Hz rTMS 治疗 3 周。行为学结果评估包括蔗糖偏好测试、强迫游泳测试和旷场测试。组织学分析侧重于细胞凋亡、GFAP 和 FGF2 的表达以及 FGF2 途径相关蛋白。结果表明，rTMS 治疗后，大鼠的蔗糖偏好增加，旷场表现改善，强迫游泳的不动时间减少。rTMS 治疗大鼠的行为变化伴随着 TUNEL 阳性神经细胞数量的明显减少和 BAX 表达水平的降低，以及 Bcl2 的增加。此外，GFAP 和 FGF2 的表达增加，同时 FGF2 下游途径被激活。这些结果表明，rTMS 治疗可以改善抑郁样行为，减轻神经细胞凋亡，并逆转抑郁大鼠模型中星形胶质细胞的减少。我们假设 rTMS 在 CUMS 诱导大鼠中的治疗作用与 FGF2/FGFR1/p-ERK 信号通路的激活有关。
