Multi-omics analysis of pathological changes in the amygdala of rats subjected to chronic restraint stress

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.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.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.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.