Depression is a serious mental illness. Previous studies found that early life stress (ELS) plays a vital role in the onset and progression of depression. However, relevant studies have not yet been able to explain the specific effects of early stress on stress-induced depression sensitivity and individual behavior during growth. Therefore, we constructed a maternal separation (MS) model and administered chronic social frustration stress at different stages of their growth while conducting metabolomics analysis on the hippocampus of mice. Our results showed that the immobility time of mice in the forced swimming test was significantly reduced at the end of MS. Meanwhile, mice with MS experience significantly decreased total movement distance in the open field test and sucrose preference ratio in the sucrose preference test when subjected to chronic social defeat stress (CSDS) during adolescence. In adulthood, the results were the opposite. In addition, we found that level changes in metabolites such as Beta-alanine, l-aspartic acid, 2-aminoadipic acid, and Glycine are closely related to behavioral changes. These metabolites are mainly enriched in Pantothenate, CoA biosynthesis, and Beta Alanine metabolism pathways. Our experiment revealed that the effects of ELS vary across different age groups. It will increase an individual's sensitivity to depression when facing CSDS in adolescence, but it will reduce their sensitivity to depression when facing CSDS in adulthood. This may be achieved by regulating the hippocampus's Pantothenate and CoA biosynthesis and Beta Alanine metabolism pathways represented by Beta-alanine, l-Aspartic acid, 2-aminoadipic acid, and Glycine metabolites.

中文翻译：

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母亲分离通过影响海马代谢调节小鼠应激性抑郁的敏感性

抑郁症是一种严重的精神疾病。先前的研究发现，早期生活压力（ELS）在抑郁症的发病和进展中起着至关重要的作用。然而，相关研究尚未能够解释早期压力对压力诱发的抑郁敏感性和成长过程中个体行为的具体影响。因此，我们构建了母体分离（MS）模型，并在其生长的不同阶段对其进行慢性社交挫折应激，同时对小鼠海马体进行代谢组学分析。我们的结果表明，强迫游泳试验中小鼠的不动时间在 MS 结束时显着减少。同时，患有多发性硬化症的小鼠在青春期遭受慢性社交失败压力（CSDS）时，在旷场测试中的总运动距离和蔗糖偏好测试中的蔗糖偏好比显着降低。成年后，结果却恰恰相反。此外，我们发现β-丙氨酸、L-天冬氨酸、2-氨基己二酸和甘氨酸等代谢物的水平变化与行为变化密切相关。这些代谢物主要富集于泛酸、CoA生物合成和β-丙氨酸代谢途径。我们的实验表明，ELS 的效果因不同年龄组而异。当个体在青春期面对CSDS时，它会增加个体对抑郁的敏感性，但当个体在成年期面对CSDS时，它会降低个体对抑郁的敏感性。这可以通过调节海马的泛酸和CoA生物合成以及以β-丙氨酸、L-天冬氨酸、2-氨基己二酸和甘氨酸代谢物为代表的β-丙氨酸代谢途径来实现。