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Hong Xu,1 Zuoli Sun,1 Gang Wang,1,2 Rena Li1 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Gang Wang; Rena Li, Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, People’s Republic of China, Email gangwangdoc@ccmu.edu.cn; renali@ccmu.edu.cnBackground: Several clinical studies have examined the connection between depression and bone loss, but the cause-and-effect relationship between the two conditions, especially in animal models, is not well-studied.Methods: A total of 32 female mice were, randomly divided into control group (CON, n=19) and depression group (DEP, n=13). The mice in the DEP group were subjected to 21 consecutive days of restraint stress, following depressive-like behaviors were assessment. The femurs were collected using Micro-Computed Tomography (μCT) and histochemical staining. In parallel, levels of serotonin-related proteins in the brain were measured using Western blot analysis, and sex hormone profiles were determined through liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).Results: The mice in the DEP group exhibited clear signs of depressive-like behaviors and an increase in serotonin transporter levels (t=-2.435, P< 0.05). In comparison to the CON mice, the DEP mice showed a decrease in bone mineral density (t =3.741, P< 0.05), bone surface area density (t =8.009, P< 0.01), percent bone volume (t =4.293, P< 0.05), trabecular number (t =5.844, P< 0.01), and connected density (t =11.000, P< 0.05). Additionally, there was an increase in trabecular separation (t =-7.436, P< 0.01) in DEP mice. Furthermore, the DEP mice displayed a significant reduction in serum estrogen levels (t =4.340, P< 0.05) and changes in its metabolite (t =-3.325, P< 0.05), while the levels of androgens remained unchanged.Conclusion: The restraint stress not only led to the development of depressive-like behaviors but also disrupted the estrogen metabolism pathway, resulting in damage to bone mass and microstructure in female mice. These findings suggest that stress-induced depression may pose a risk for bone loss in female mice by altering estrogen metabolism pathways.Keywords: depression, bone mineral density, bone structure, estrogen, female |
