抑郁症易感性差异与海马CA3区及DG内树突棘数量变化的相关性研究

Stereological study on the relationship between the differences in stress susceptibility and dendritic spines changes in the CA3 and DG of hippocampal formation in depression

目的:探讨在慢性不可预知性应激(chronic unpredictable stress,CUS)模型中压力耐受大鼠海马结构CA3及海马齿状回(dentate gyrus,DG)内树突棘数量的改变情况,以期深入了解抑郁症发病的结构基础。方法:选用4~5周龄雄性spraguedawley(SD)大鼠,将糖水偏好稳定的大鼠随机分为空白对照组和CUS造模组,造模组采取孤养并给予4周的CUS干预。根据糖水偏好结果筛选出CUS敏感组和CUS耐受组。利用免疫组织化学结合体视学方法对每组抽选出的5只大鼠海马结构CA3和DG内的树突棘数量进行精确的三维定量研究。结果:与空白对照组、CUS耐受组相比,CUS敏感组的糖水偏好百分比均明显下降(P=0.000,P=0.000),而空白对照组与CUS耐受组的糖水偏好百分比无明显差异(P=0.262);与空白对照组和CUS耐受组相比较,CUS敏感组大鼠海马结构CA3区内的树突棘数量明显下降(P=0.008,P=0.004),CUS敏感组大鼠海马结构DG区内的树突棘数量也明显下降(P=0.001,P=0.001);而在大鼠海马结构CA3及DG内,CUS耐受组与空白对照组的树突棘总数目无明显差异(P=0.656,P=0.950)。结论:CUS耐受组大鼠海马结构CA3及DG内树突棘的数量不受CUS干预的影响,提示海马结构内树突棘数量可能是抑郁症易感性差异的关键因素之一,为抑郁症的治疗提供了新的方向。

Objective：To investigate the differences of dendritic spines in the CA3 and dentate gyrus （DG） of the hippocampal forma- tion in normal control group, chronic unpredictable stress （CUS） susceptibility group and CUS resistance group in order to further un- derstand the structural bases of the depression-like behaviors. Methods ：Four-five weeks old male SD rats were randomly divided into normal control group and model group. The model group rats were treated with chronic unpredictable stress for 4 weeks. Then,themodel group rats were randomly divided into the CUS resis- tance group and the CUS susceptibility group according to the results of sucrose preference test. The numbers of dendritic spines in the CA3 and DG of the hippocampal formation of normal control （n=5）, CUS susceptibility group （n=5） and CUS resistance group （n=5） were quantitatively estimated using the stereological methods and immunohistochemical methods.Results：The sucrose preference in the CUS susceptibility group rats was significantly decreased when compered with that of the CUS resistance group and normal control group （P=0.000,P=0.000）. The sucrose preference in the CLIS resistance group and normal con- trol group was not significantly different（P=0.262）. The total number of the dendritic spines in the CA3 of the CUS susceptibility group rats was significantly lower than that of the normal control group and that of the CUS resistance group（P=0.008,P=-0.004）. The total number of the dendritic spines in the DG of the CUS susceptibility group rats was significantly lower than that of the normal control group and that of the CUS resistance group（P=0.001 ,P=-01001 ）, The total number of the dendritic spines in the CA3 and DG in the normal control group was not significantly different when compared with that of the CUS resistance group（P=0.656,P=-0.950）. Conclusion ：The total number of the dendritic spines in the CA3 and DG of the hippocampal formation in the CUS resistance group was not affected by CUS intervention, suggesting that the number of dendritic spines in hippocampus might be one of the key factors for the difference of stress susceptibility in depression. Our study might provide one of the important structural bases for searching the new treatment direction of depression.