Neuroprotective efficacy of different levels of high-frequency repetitive transcranial magnetic stimulation in mice with CUMS-induced depression: Involvement of the p11/BDNF/Homer1a signaling pathway.
Neuroprotective efficacy of different levels of high-frequency repetitive transcranial magnetic stimulation in mice with CUMS-induced depression: Involvement of the p11/BDNF/Homer1a signaling pathway.
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DOI：
10.1016/j.jpsychires.2020.03.018
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发表时间：
2020-04
影响因子：
4.8
通讯作者：
Chengchao Zuo;Huan Cao;Fengfei Ding;Jianling Zhao;Yaqi Huang;Guo Li;Shanshan Huang;Hong Jiang-Hong-Jia
中科院分区：
文献类型：
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作者：
Chengchao Zuo;Huan Cao;Fengfei Ding;Jianling Zhao;Yaqi Huang;Guo Li;Shanshan Huang;Hong Jiang-Hong-Jia
高频重复经颅磁刺激（HF-rTMS）广泛用于治疗抑郁症。然而，潜在的机制尚未确定，并且刺激参数（尤其是刺激频率）的最佳选择存在不确定性。我们之前对小鼠的研究表明，10 Hz HF-rTMS 通过诱导 Homer1a 的表达并降低皮质锥体细胞的兴奋性来改善抑郁症。本研究的目的是比较 15 Hz 和 25 Hz HF-rTMS 在慢性不可预测轻度应激 (CUMS) 诱发抑郁症模型中的效果，并探讨其可能的分子机制。雄性 C57BL/6J 小鼠接受 CUMS 治疗 28 天，然后接受 15 Hz 和 25 Hz rTMS 治疗 4 周。蔗糖偏好、开放场地、强迫游泳和悬尾测试用于评估抑郁样行为。进行免疫染色来测量神经元损失和神经发生。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细胞凋亡。使用蛋白质印迹检查突触相关蛋白的表达以及 HF-rTMS 对信号通路的影响。结果显示，15赫兹和25赫兹rTMS均具有显着的抗抑郁作用； 15-Hz rTMS 在防止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。这些研究结果表明，15 Hz 和 25 Hz HF-rTMS 可以通过多个角度发挥不同程度的神经保护作用，其中至少部分涉及 p11/BDNF/Homer1a 通路。
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.