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加速连续θ波爆发刺激对慢性束缚应激小鼠的抗焦虑作用及其涉及肠道微生物群的潜在机制

Anxiolytic effects of accelerated continuous theta burst stimulation on mice exposed to chronic restraint stress and the underlying mechanism involving gut microbiota.

作者信息

Wang Yihan, Guo Cong, Zang Bowen, Wang Peng, Yang Chuyan, Shi Ruifeng, Kong Yue, Sui Aoran, Li Shao, Lin Yongzhong

机构信息

Department of Neurology, The Second Hospital of Dalian Medical University, Dalian 116021, China.

Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian 116044, China.

出版信息

J Affect Disord. 2025 Apr 15;375:49-63. doi: 10.1016/j.jad.2025.01.104. Epub 2025 Jan 21.

DOI:10.1016/j.jad.2025.01.104
PMID:39848468
Abstract

BACKGROUND

Accelerated continuous theta burst stimulation (acTBS) is a more intensive and rapid protocol than continuous theta burst stimulation (cTBS). However, it remains uncertain whether acTBS exhibits anxiolytic effects. The aim of this study was to investigate the impact of acTBS on anxiety model mice and elucidate the underlying mechanisms involved, in order to provide a more comprehensive understanding of its effects.

METHODS

Chronic restraint stress (CRS) model was employed to observe the anxiolytic effects of acTBS. The study focused on evaluating the impact of acTBS on behavior, neuroinflammation, gut and gut microbiota in mice with anxiety induced by CRS.

RESULTS

The application of acTBS ameliorated anxiety-like behaviors in CRS-induced mice. Notably, it effectively suppressed the activation of microglia and reduced the level pro-inflammatory cytokines in PFC, hippocampus, and amygdala of anxiety mice. Additionally, acTBS alleviated astrocyte activation specifically in hippocampus. The NF-κB signaling pathway involved in the anti-inflammatory effects of acTBS. Furthermore, acTBS ameliorated inflammation and histological damage in colon. 16S rRNA analysis revealed that acTBS significantly enhanced the relative abundance of Lactobacillus, while normalized the dysregulated levels of Coriobacterales, Bacteroides, and Parabacteroides caused by CRS. These changes facilitated chemoheterotrophic and fermentation functions within the microbiota. Importantly, changes in microbiota composition influenced by acTBS was found to be correlated with anxiety-like behaviors and neuroinflammation.

CONCLUSIONS

acTBS exerted anxiolytic effects on mice exposed to CRS, which was associated with the modulation of gut microbiota.

摘要

背景

加速连续θ波爆发刺激(acTBS)是一种比连续θ波爆发刺激(cTBS)更强烈、更快速的方案。然而,acTBS是否具有抗焦虑作用仍不确定。本研究的目的是探讨acTBS对焦虑模型小鼠的影响,并阐明其潜在机制,以便更全面地了解其作用。

方法

采用慢性束缚应激(CRS)模型观察acTBS的抗焦虑作用。该研究重点评估acTBS对CRS诱导的焦虑小鼠的行为、神经炎症、肠道和肠道微生物群的影响。

结果

应用acTBS可改善CRS诱导小鼠的焦虑样行为。值得注意的是,它有效抑制了小胶质细胞的激活,并降低了焦虑小鼠前额叶皮质、海马体和杏仁核中促炎细胞因子的水平。此外,acTBS特异性减轻了海马体中星形胶质细胞的激活。NF-κB信号通路参与了acTBS的抗炎作用。此外,acTBS改善了结肠的炎症和组织学损伤。16S rRNA分析显示,acTBS显著提高了乳酸杆菌的相对丰度,同时使CRS引起的科里杆菌目、拟杆菌属和副拟杆菌属的失调水平正常化。这些变化促进了微生物群内的化学异养和发酵功能。重要的是,发现受acTBS影响的微生物群组成变化与焦虑样行为和神经炎症相关。

结论

acTBS对暴露于CRS的小鼠具有抗焦虑作用,这与肠道微生物群的调节有关。

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