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 (=-2.435, < 0.05). In comparison to the CON mice, the DEP mice showed a decrease in bone mineral density ( =3.741, < 0.05), bone surface area density ( =8.009, <0.01), percent bone volume ( =4.293, < 0.05), trabecular number ( =5.844, <0.01), and connected density ( =11.000, < 0.05). Additionally, there was an increase in trabecular separation ( =-7.436, <0.01) in DEP mice. Furthermore, the DEP mice displayed a significant reduction in serum estrogen levels ( =4.340, < 0.05) and changes in its metabolite ( =-3.325, < 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.