■一些临床研究已经检查了抑郁症和骨质流失之间的联系,但是这两个条件之间的因果关系,尤其是在动物模型中,没有得到很好的研究。
■总共32只雌性小鼠,随机分为对照组(CON,n=19)和抑郁组(DEP,n=13)。DEP组小鼠连续进行21天的束缚应激,以下是抑郁样行为的评估。使用微计算机断层扫描(μCT)和组织化学染色收集股骨。并行,使用蛋白质印迹分析测量大脑中5-羟色胺相关蛋白的水平,通过液相色谱-质谱/质谱(LC-MS/MS)测定性激素谱。
■DEP组小鼠表现出明显的抑郁样行为和5-羟色胺转运体水平升高(t=-2.435,P<0.05)。与CON小鼠相比,DEP小鼠骨密度下降(t=3.741,P<0.05),骨表面积密度(t=8.009,P<0.01),骨体积百分比(t=4.293,P<0.05),骨小梁数(t=5.844,P<0.01),连通密度(t=11.000,P<0.05)。此外,DEP小鼠骨小梁间距增加(t=-7.436,P<0.01)。此外,DEP小鼠血清雌激素水平显著降低(t=4.340,P<0.05),代谢产物显著改变(t=-3.325,P<0.05),而雄激素水平保持不变。
■束缚应激不仅导致抑郁样行为的发展,而且破坏了雌激素代谢途径,导致雌性小鼠骨量和显微结构受损。这些发现表明,应激诱导的抑郁症可能通过改变雌激素代谢途径而对雌性小鼠造成骨质流失的风险。
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.