产前慢性应激对子代大鼠学习记忆和海马神经元树突棘的影响

Influence of pregnant rats＇ prenatal chronic stress on hippocampal dendritic spines and the function of learning and memory in their offsprings

目的 研究孕鼠产前慢性应激（PS）对子代大鼠学习记忆的影响及其可能的分子机制.方法 通过SD孕鼠妊娠第14-21天每天进行3次束缚,每次45 min,建立PS模型,仔鼠为研究对象标记为PS组,无束缚孕鼠的仔鼠为对照组,每组又分为雌雄组,各20只.利用Morris水迷宫分析系统检测学习记忆能力,放射免疫法测定血清基础皮质酮（COR）和促皮质素（ACTH）水平,通过高尔基染色法观察海马CA1区神经元树突棘的形态和密度变化,并进行统计学分析.结果 在Morris水迷宫测试中,雌性PS组的逃逸潜伏期（EL）明显长于雌性对照组,差异具有统计学意义（F =4.533,P＜0.05）;第5天的EL差异具有统计学意义（=2.788,P＜0.01）.雄性PS组的EL明显长于雄性对照组,差异具有统计学意义（F=6.101,P＜0.05）;第2天EL差异具有统计学意义（t =3.051,P＜0.01）.在空间探索实验中,PS组的目标象限停留时间与同性别对照组相似,差异无统计学意义（P＞0.05）.PS组子代雌性大鼠的血清基础COR水平较同性别对照组升高,差异具有统计学意义（t =3.658,P＜0.01）;PS组子代雄性大鼠的血清基础ACTH水平较同性别对照组升高,差异具有统计学意义（t=2.319,P ＜0.05）.高尔基染色显示PS组仔鼠海马CA1区锥体神经元树突形态简单化,表现为树突分支减少,树突棘密度减少,与对照组比较差异具有统计学意义（t=-3.072,P＜0.01）.结论 孕鼠产前慢性束缚应激引起仔鼠下丘脑-垂体-肾上腺轴功能紊乱,损害仔鼠空间学习记忆能力,可能与仔鼠海马CA1区神经元树突棘的形态变化和密度降低有关.

Objective To study the influence of pregnant rats＇ prenatal chronic stress （PS） on learning and memory of their offspring rats and its possible molecular mechanisms.Methods Pregnant females were individually restrained for 45 min 3 times a day during pregnancy from day 14 to day 21.Control pregnant females were left undisturbed in their home cages.The rat offsprings were randomly assigned to PS group or control group.Males and females were kept for the study separately.The learning and memory of the developing rat offspring in the Morris water maze were examined.The basal levels of corticosterone （COR） and adreno-cortico-tropic-hormone （ACTH） were analyzed by using radioimmunoassay.The Golgi-Cox impregnation technique was used to compare density and morphology of the CA1 hippocampal dendritic spines.Results The escape latency （EL） to find the platform in the control group was significantly less than that in the PS group in female rat offspring （F =4.533,P 〈 0.05）,and the difference was statistically significant on the 5^th day （t =2.788,P 〈 0.01）.EL to find the platform in the control group was significantly less than that in the PS group in male rat offspring （F =6.101,P 〈0.05）,and the difference was statistically significant on the second day （t =3.051,P 〈 0.01）.In the space exploration experiments of the water maze,the retention time observed for the control group and the PS group in the goal quadrant was similar（P 〉 0.05）.The basal levels of the serum COR in the PS group were higher than those in the control group of female rat offspring（t =3.658,P 〈 0.01） and the basal levels of the serum ACTH in the PS group were higher than those in the control group of male rat offsprings（t =2.319,P 〈 0.05）.A simplified pattern was observed in the CA1 hippocampal dendritic spines in the PS group,showing a less extent of dendritic arborization and the density was significantly lower than that in the control group（t =-3.072,P 〈 0.01）.Conclusions Altered function of the hypothalamic-pituitary-adrenal axis in the offspring mediates the cognitive alterations observed following prenatal stress should to be associated with the lower density and simplified pattern of CA1 dendritic spines.