The Impact of Depression on Detrimental Changes in Bone Microstructure in Female Mice

Background: 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.