High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is widely used to treat depression. However, the underlying mechanism has not been identified, and there is uncertainty regarding the optimal choice of stimulus parameters, especially stimulus frequency. Our previous study in mice demonstrated that 10-Hz HF-rTMS ameliorated depression by inducing expression of Homer1a and reducing excitability of cortical pyramidal cells. The aims of this study were to compare the effects of 15-Hz and 25-Hz HF-rTMS in a model of chronic unpredictable mild stress (CUMS)-induced depression and investigate its possible molecular mechanism. Male C57BL/6J mice were treated with CUMS for 28 days followed by 15-Hz and 25-Hz rTMS for 4 weeks. The sucrose preference, open field, forced swimming, and tail suspension tests were used to evaluate depression-like behaviors. Immunostaining was performed to measure neuronal loss and neurogenesis. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Expression of synapse-related proteins and the effects of HF-rTMS on the signaling pathway were examined using Western blot. The results showed that both 15-Hz and 25-Hz rTMS had significant antidepressant effects; 15-Hz rTMS seemed to be more effective than 25-Hz rTMS in preventing neuronal loss and promoting neurogenesis, while 25-Hz rTMS was superior to 15-Hz rTMS in facilitating synaptic plasticity. We also found that 15-Hz and 25-Hz rTMS markedly increased expression of p11, BDNF, Homer1a, and p-trkB proteins. These findings suggest that 15-Hz and 25-Hz HF-rTMS could exert neuroprotective effects to different degrees via multiple perspectives, which at least in part involve the p11/BDNF/Homer1a pathway.

中文翻译：

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不同水平的高频重复经颅磁刺激对CUMS诱发的抑郁症小鼠的神经保护功效：涉及p11 / BDNF / Homer1a信号通路。

高频重复经颅磁刺激（HF-rTMS）被广泛用于治疗抑郁症。但是，尚未发现潜在的机制，并且关于刺激参数，尤其是刺激频率的最佳选择还存在不确定性。我们先前在小鼠中的研究表明，通过诱导Homer1a的表达并降低皮质锥体细胞的兴奋性，10 Hz HF-rTMS可减轻抑郁症。这项研究的目的是在慢性不可预测的轻度应激（CUMS）诱发的抑郁症模型中比较15 Hz和25 Hz HF-rTMS的影响，并研究其可能的分子机制。雄性C57BL / 6J小鼠用CUMS治疗28天，然后用15 Hz和25 Hz rTMS治疗4周。蔗糖偏爱，旷野，强迫游泳，尾部悬挂测试用于评估类似抑郁的行为。进行免疫染色以测量神经元丢失和神经发生。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色检测凋亡。使用蛋白质印迹法检测突触相关蛋白的表达以及HF-rTMS对信号通路的影响。结果表明，15 Hz和25 Hz rTMS均具有显着的抗抑郁作用。15 Hz rTMS在预防神经元丢失和促进神经发生方面似乎比25 Hz rTMS更有效，而25 Hz rTMS在促进突触可塑性方面优于15 Hz rTMS。我们还发现15 Hz和25 Hz rTMS显着增加了p11，BDNF，Homer1a和p-trkB蛋白的表达。