Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan 430030, Hubei, China.
Department of Neurology, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, China.
Int Immunopharmacol. 2022 Aug;109:108788. doi: 10.1016/j.intimp.2022.108788. Epub 2022 Apr 30.
Recently numerous studies have demonstrated that neuroinflammation plays a critical role in the pathogenesis of depression. Repetitive transcranial magnetic stimulation (rTMS) has been used to treat depression for years but its mechanism is not fully elucidated. The present study was designed to investigate whether rTMS could alleviate neuroglia-associated neuro-inflammatory process in mice models of depression.
Mice were treated with chronic unpredictable mild stress (CUMS) to induce depression models and received four weeks of 15 Hz rTMS. Then the depression-like behaviors, microglia activation, the level of astrocytes, pro-inflammatory cytokines and inflammation-related signaling pathways were evaluated.
rTMS ameliorated depression-like behaviors in CUMS-treated mice. rTMS not only markedly alleviated the activation of microglia but induced a switch of microglia polarization from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype in the hippocampus and prefrontal cortex. Meanwhile, rTMS reversed the down-regulation of astrocytes and inhibited high levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-alpha (TNF-α) caused by CUMS in above regions. Moreover, we found that anti-inflammatory actions by rTMS were associated with the TLR4/NF-κB/NLRP3 signaling pathway.
Collectively, our findings indicate that rTMS can exert anti-inflammatory actions in depression and provide new insights into the mechanism of rTMS in the treatment of depression.
最近大量研究表明神经炎症在抑郁症的发病机制中起着关键作用。重复经颅磁刺激(rTMS)已被用于治疗抑郁症多年，但它的机制尚未完全阐明。本研究旨在探讨 rTMS 是否能减轻抑郁模型小鼠神经胶质相关神经炎症过程。
用慢性不可预测轻度应激(CUMS)处理小鼠以诱导抑郁模型，并接受四周的 15Hz rTMS 治疗。然后评估抑郁样行为、小胶质细胞激活、星形胶质细胞水平、促炎细胞因子和炎症相关信号通路。
rTMS 改善了 CUMS 处理小鼠的抑郁样行为。rTMS 不仅显著减轻了小胶质细胞的激活，而且在海马体和前额叶皮质中诱导了小胶质细胞从促炎 M1 表型向抗炎 M2 表型的极化转变。同时，rTMS 逆转了 CUMS 引起的上述区域星形胶质细胞下调，并抑制了白细胞介素(IL)-6、IL-1β和肿瘤坏死因子-α(TNF-α)的高水平。此外，我们发现 rTMS 的抗炎作用与 TLR4/NF-κB/NLRP3 信号通路有关。
综上所述，我们的研究结果表明 rTMS 可在抑郁症中发挥抗炎作用，并为 rTMS 治疗抑郁症的机制提供了新的见解。
