Objective

Overwhelming stress potentially results in the occurrence of many mental diseases. The amygdala is one region in the brain targeted by stress. Recent studies have shown that changes in the amygdala of subjects under stress are related to depression, anxiety and post-traumatic stress disorder (PTSD). However, researchers have not clearly elucidated the changes in the amygdala in response to stress and the underlying mechanism. We conducted several experiments to understand this mechanism.

Methods

In this study, we first established a rat model of chronic restraint stress (CRS) and observed the changes in behavior and neurons in the amygdala. Second, an integrated metabolomics and proteomics experiment was conducted to identify potential stress-related biomarkers. Finally, we validated two molecules of interest and detected four apoptosis-related proteins using Western blotting to further determine the related mechanisms.

Results

Our study revealed the presence of anxiety-like behaviors and pathological changes in amygdalar neurons in the rat model. In the multi-omics analysis, 19 potential molecules were identified. Western blotting confirmed consistent changes in the levels of Cry1 and Brcc36 obtained in previous results. The levels of proteins in the ataxia telangiectasia mutated (ATM) pathway were increased in the CRS group.

Conclusions

CRS causes anxiety-like behaviors that are potentially related to decreased levels of GABA in the amygdala. Moreover, CRS potentially alters the levels of Cry1 and Brcc36 and results in circadian rhythm disorder and impairments in DNA repair and apoptosis in the amygdala through a mechanism mediated by the ATM pathway.

中文翻译：

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慢性束缚应激大鼠杏仁核病理变化的多组学分析[J].

客观的

压倒性的压力可能会导致许多精神疾病的发生。杏仁核是大脑中受压力影响的区域之一。最近的研究表明，处于压力下的受试者杏仁核的变化与抑郁、焦虑和创伤后应激障碍（PTSD）有关。然而，研究人员还没有清楚地阐明杏仁核响应压力的变化及其潜在机制。我们进行了几次实验来理解这种机制。

方法

在这项研究中，我们首先建立了慢性束缚应激（CRS）大鼠模型，并观察了杏仁核中行为和神经元的变化。其次，进行了综合代谢组学和蛋白质组学实验，以确定潜在的压力相关生物标志物。最后，我们验证了两个感兴趣的分子，并使用蛋白质印迹法检测了四种凋亡相关蛋白，以进一步确定相关机制。

结果

我们的研究揭示了大鼠模型中杏仁核神经元存在焦虑样行为和病理变化。在多组学分析中，确定了 19 个潜在分子。蛋白质印迹证实了先前结果中获得的 Cry1 和 Brcc36 水平的一致变化。在 CRS 组中，共济失调毛细血管扩张突变 (ATM) 通路中的蛋白质水平增加。

结论

CRS 会导致类似焦虑的行为，这可能与杏仁核中 GABA 水平降低有关。此外，CRS 可能通过 ATM 通路介导的机制改变 Cry1 和 Brcc36 的水平，并导致昼夜节律紊乱和杏仁核 DNA 修复和细胞凋亡受损。