电休克治疗抑郁症的微生物-肠-脑轴调节机制

Jiaming Ji, Jinyan Guo, Jirong Yang, Siyang Zeng, Xue Han, Ziqing Hei, Weifeng Yao, Chaojin Chen
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引用次数: 0

摘要

目的探讨电休克治疗(ECT)对抑郁行为的影响。此外,我们还探索了ECT通过微生物-肠道-脑轴改变肠道微生物群组成和功能的机制。方法采用慢性不可预测轻度应激法建立小鼠抑郁模型。这些小鼠被分为三组:对照组、抑郁症组和ect治疗组。通过一系列的行为测试来评估抑郁行为,包括监测体重、野外测试、蔗糖偏好和强迫游泳测试。采用苏木精和伊红(H&;E)染色、尼氏染色和免疫荧光法以及激光散斑造影对脑组织和肠道组织进行组织学和微循环评估。此外,采用酶联免疫吸附法测定肠道组织中炎症因子肿瘤坏死因子-α (TNF-α)、白细胞介素-6 (IL-6)和白细胞介素-1β (IL-1β)的含量。采用宏基因组测序来评估肠道微生物群的多样性和丰度。结果在强迫游泳测试中,ect显著改善了小鼠的抑郁行为,证明了体重增加和静止时间减少。H&;E染色显示肠道炎症明显减少,而尼索染色显示ECT治疗后神经元形态恢复。此外,免疫荧光分析显示海马区c-Fos表达升高(P < 0.05)。炎症因子评估显示ECT组TNF-α、IL-6和IL-1β水平显著降低。此外,宏基因组测序显示ECT增强了肠道微生物群的多样性,特别是恢复了Bacteroides和Verrucomicrobia的丰度(P < 0.05)。结论ect通过调节肠道菌群,增强肠脑轴功能发挥抗抑郁作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mechanisms of microbial-gut-brain axis modulation by electroconvulsive therapy in the treatment of depression

Purpose

The present study aims to evaluate the effects of electroconvulsive therapy (ECT) on depressive behaviors. In addition, we explore mechanisms by which ECT alters the composition and functioning of gut microbiota through the microbiota-gut-brain axis.

Methods

A depression model in mice was established using chronic unpredictable mild stress. The mice were divided into three groups: control, depression, and ECT-treated. Depressive behaviors were assessed through a series of behavioral tests, including monitoring body weight, open field tests, sucrose preference and forced swim tests. Histological and microcirculatory assessments of brain and gut tissues were conducted using hematoxylin and eosin (H&E) staining, Nissl staining and immunofluorescence methodology along with laser speckle contrast imaging. In addition, the inflammatory cytokines Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6) and Interleukin-1β (IL-1β) were quantified in gut tissues using enzyme-linked immunosorbent assay. Metagenomic sequencing was employed to evaluate the diversity and abundance of the gut microbiota.

Results

ECT significantly improved depressive behaviors in mice as evidenced by increased body weight and decreased immobility time in the forced swim tests. H&E staining indicated a substantial reduction in gut inflammation while Nissl staining revealed a restoration of neuronal morphology following ECT treatment. Furthermore, immunofluorescence analysis showed elevated c-Fos expression in the hippocampal region (P < 0.05). Assessments of inflammatory cytokines demonstrated significant reductions in TNF-α, IL-6, and IL-1β levels in the ECT group. In addition, metagenomic sequencing showed that ECT enhanced gut microbiota diversity, particularly restoring the abundance of Bacteroides and Verrucomicrobia (P < 0.05).

Conclusion

ECT exerts its antidepressant effects by modulating gut microbiota and enhancing the functionality of the gut-brain axis.

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