Chronic unpredictable mild stress produces depressive-like behavior, hypercortisolemia, and metabolic dysfunction in adolescent cynomolgus monkeys.
Chronic unpredictable mild stress produces depressive-like behavior, hypercortisolemia, and metabolic dysfunction in adolescent cynomolgus monkeys.
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慢性不可预测的轻度压力会导致青少年食蟹猴出现抑郁样行为、高皮质醇血症和代谢功能障碍
DOI：
10.1038/s41398-020-01132-6
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发表时间：
2021-01-04
影响因子：
6.8
通讯作者：
Xie P
中科院分区：
文献类型：
--
作者：
Teng T;Shively CA;Li X;Jiang X;Neigh GN;Yin B;Zhang Y;Fan L;Xiang Y;Wang M;Liu X;Qin M;Zhou X;Xie P
青少年抑郁症是一种常见而严重的精神障碍，具有不同于成人抑郁症的独特特征。成年非人灵长类动物应激诱导的抑郁样行为模型是研究抑郁行为机制的极佳模型；然而，青少年非人灵长类动物模型仍然缺乏。10只雄性青春期食蟹猴按年龄和体重配对分为慢性不可预测轻度应激(CMS，n= 5)组和对照组(CON，n= 5)。CUMS组在55天内暴露于多种不可预测的温和应激源，持续5个周期。在基线时，CUMS组和CON组之间没有差异。在终点，与CON组相比，CUMS组表现出显著更高的抑郁样行为(抱抱姿势)，而显著低于CON组。此外，在CUMS组中，抑郁样行为从基线到终点逐渐增加，但在CON组中没有改变。在苹果测试中，CUMS组尝试苹果的次数明显少于CON组。在人类入侵者测试中，CUMS组在凝视阶段表现出的焦虑样行为明显高于CON组。在终点，CUMS组的头发皮质醇水平显著高于CON组，而且从基线到终点也是升高的。终点时的血浆代谢谱发现代谢物途径的改变与青少年抑郁症患者的代谢途径重叠。CUMS可诱发青春期食蟹猴的抑郁和焦虑样行为、高皮质醇血症和代谢紊乱。这是一个很有前途的模型，可以用来研究青少年抑郁的机制。
Adolescent depression is a common and serious mental disorder with unique characteristics that are distinct from adult depression. The adult non-human primate stress-induced model of depressive-like behavior is an excellent model for the study of mechanisms; however, an adolescent nonhuman primate model is still lacking. Ten male adolescent cynomolgus monkeys were divided into a chronic unpredictable mild stress (CUMS,n= 5) group and a control (CON,n= 5) group by age and weight-matched pairs. The CUMS group was exposed to multiple unpredictable mild stressors for five cycles over 55 days. At baseline, there were no differences between CUMS and CON groups. At endpoint, the CUMS group demonstrated significantly higher depressive-like behavior (huddle posture), and significantly lower locomotion compared with the CON group. Furthermore, depressive-like behavior increased from baseline to endpoint in the CUMS group, but not changed in the CON group. In the attempt for apple test, the CUMS group made significantly fewer attempts for the apple than the CON group. In the human intruder test, the CUMS group showed significantly higher anxiety-like behaviors in the stare phase than the CON group. Hair cortisol level was significantly higher in the CUMS group than the CON group at endpoint, and was also elevated from baseline to endpoint. Metabolic profiling of plasma at endpoint identified alterations in metabolite pathways which overlapped with those of adolescent depression patients. CUMS can induce depressive-like and anxiety-like behaviors, hypercortisolemia, and metabolic perturbations in adolescent cynomolgus monkeys. This is a promising model to study the mechanisms underlying adolescent depression.
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