小鼠海马结构与脊髓损伤后抑郁症高发病率的关系研究

目的:探究脊髓损伤引发的抑郁高风险率是否与海马生理结构的改变有关。方法:制作小鼠脊髓损伤模型,分别在损伤后不同时期采用Basso Mouse Scale(BMS)评分对小鼠术后运动功能进行评估;并通过糖水偏好实验和悬尾实验评估小鼠的抑郁情况;HE染色观察海马组织内部细胞的变化;电镜观察海马亚细胞结构突触的结构变化;RT-qPCR检测突触蛋白标志物突触小泡蛋白(SYP)和突触后致密蛋白95(PSD-95)在mRNA水平上的变化。结果:行为学实验显示模型组小鼠有显著的抑郁行为,且在第7天抑郁程度最显著(P<0.01);HE染色显示,与对照组相比,模型组海马细胞排列紊乱,数量减少,形态欠规则;电镜结果显示,与对照组相比,模型组海马超微结构突触数量减少,突触活动区长度变短,突触后致密物厚度变薄,突触间隙宽度增加,突触界面曲率减小(P<0.05);RT-qPCR结果显示模型组SYP和PSD-95 mRNA表达水平较对照组降低(P<0.05)。结论:海马生理结构的改变是脊髓损伤后抑郁症高风险的原因之一。

Relationship between hippocampal structure and high incidence of depression after spinal cord injury in mice

AIM: To explore whether the high risk of depression caused by spinal cord injury is related to structural changes of hippocampus. METHODS: Mouse spinal cord injury model was established. The Basso Mouse Scale(BMS) was used to evaluate the postoperative motor function of mice at different periods after injury. The depression of mice was evaluated by behavior experiment. The morphological changes of cells in hippocampal tissue were observed by HE staining. The structural changes of hippocampal subcellular synapses were observed by electron microscopy. RT-qPCR was used to detect the changes of synaptic protein markers synaptophysin(SYP) and postsynaptic density protein 95(PSD-95) at the mRNA level. RESULTS: The mice had significant depressive behaviors in model group, and the depression degree was the most serious on the 7 th day(P<0.01). Compared with control group, the arrangement of hippocampal cells was disordered, the cell number was decreased, and the shape was irregular in model group. Compared with control group, the observation results of electron microscopy showed that the number of synapses in the hippocampal ultrastructure was decreased, the length of synaptic activity zone was shortened, the thickness of postsynaptic density was thinned, the width of synaptic gap was increased, and the curvature of synaptic interface was decreased in the model group(P<0.05). The mRNA expression levels of SYP and PSD-95 in model group were lower than those in control group(P<0.05). CONCLUSION: The change of hippocampal structure is one of the important reasons leading to high risk of depression caused by spinal cord injury.