Repetitive transcranial magnetic stimulation (rTMS) treatment is widely accepted as an evidence-based treatment option for depression and anxiety. However, the underlying mechanism of this treatment maneuver has not been clearly understood. The chronic unpredictable mild stress (CUMS) procedure was used to establish depression and anxiety-like behavior in rats. The rTMS was performed with a commercially available stimulator for seven consecutive days, and then depression and anxiety-like behaviors were subsequently measured. The expression of nuclear factor-E2-related factor 2 (Nrf2) was measured by western-blot, and the level of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), and interleukin-6 (IL-6) was measured with Enzyme-linked immunesorbent assay (ELISA) analyzing kits. Furthermore, a small interfering RNA was employed to knockdown Nrf2, after which the neurobehavioral assessment, Nrf2 nuclear expression, and the amount of inflammation factors were evaluated. Application of rTMS exhibited a significant antidepressant and anxiolytic-like effect, which was associated with the increased Nrf2 nuclear translocation and reduced level of TNF-α, iNOS, IL-1β, and IL-6 in the hippocampus. Following Nrf2 silencing, the antidepressant and anxiolytic-like effect produced by rTMS was abolished. Moreover, the elevated Nrf2 nuclear translocation, and the reduced production of TNF-α, iNOS, IL-1β, and IL-6 in hippocampus mediated by rTMS, were reversed by Nrf2 knockdown. Together, these results reveal that the Nrf2-induced anti-inflammation effect is crucial in regulating antidepressant-related behaviors produced by rTMS.

中文翻译：

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重复经颅磁刺激通过大鼠核因子-E2 相关因子 2 介导的抗炎机制引起抗抑郁和抗焦虑样作用。

重复经颅磁刺激 (rTMS) 治疗被广泛接受为抑郁症和焦虑症的循证治疗选择。然而，这种治疗策略的潜在机制尚不清楚。慢性不可预测的轻度压力 (CUMS) 程序用于建立大鼠的抑郁和焦虑样行为。使用市售刺激器连续 7 天进行 rTMS，然后测量抑郁和焦虑样行为。Western-blot检测核因子-E2相关因子2（Nrf2）的表达，检测肿瘤坏死因子-α（TNF-α）、诱导型一氧化氮合酶（iNOS）、白细胞介素-1β（IL- 1β) 和白细胞介素 6 (IL-6) 用酶联免疫吸附试验 (ELISA) 分析试剂盒测量。此外，使用小干扰 RNA 敲低 Nrf2，然后评估神经行为评估、Nrf2 核表达和炎症因子的数量。rTMS 的应用表现出显着的抗抑郁和抗焦虑样作用，这与海马中 Nrf2 核易位增加和 TNF-α、iNOS、IL-1β 和 IL-6 水平降低有关。在 Nrf2 沉默后，rTMS 产生的抗抑郁和抗焦虑样作用被取消。此外，由 rTMS 介导的 Nrf2 核转位升高以及海马 TNF-α、iNOS、IL-1β 和 IL-6 的产生减少被 Nrf2 敲低逆转。总之，这些结果表明，Nrf2 诱导的抗炎作用对于调节 rTMS 产生的抗抑郁相关行为至关重要。