急性应激对高龄生育子代大鼠海马依赖的学习记忆的影响及其机理的研究

现代社会高龄生育（>35岁）夫妻人口不断增加，我国二孩政策的实施进一步增加高龄生育人口数量。以往研究发现高龄生育是子代患精神疾病的风险因子之一，并影响子代的认知功能。应激是不可避免的环境刺激，显著影响生物体的情感和认知功能。我们前期试验发现，大鼠的情感和认知功能显著受其亲代的生育年龄的影响，存在性别差异。长期慢性应激对大鼠的影响与生育年龄和性别存在交互作用。尤为显著的是高龄生育的雌性子代大鼠的皮质酮在急性应激后显著高于对照组，但是急性应激对大鼠高龄生育的子代的认知功能的影响及其机理尚不清楚。本研究中利用大鼠高龄生育的子代为动物模型，利用束缚应激，研究急性应激对高龄生育子代的海马依赖的恐惧记忆的影响，对海马CA1区突触传递及突触可塑性的影响，相关蛋白表达和甲基化以及激素的改变。探索生育年龄、亲代和子代的性别差异和急性应激对认知功能的交互作用及机理，为相关疾病的预防和治疗提供试验依据。

The population of advanced parental aged people increases gradually in modern society, the population increases more significantly in China because of the “second child policy”. Previous studies suggested that advanced maternal/paternal age not only was a risk factor of psychological disorder but also affect cognition in offspring. Stress, which is an unavoidable environmental stimuli in life, significantly affect emotion and cognition in livings. Our preliminary experiment found that parental age significantly affect the emotion and cognition function in rat in a gender dependent manner, chronic unpredictable mild stress (CUMS) interacted with the two factors. To our surprise, the corticosterone concentration increased significantly more in female rats of advanced parental age than those in control groups after acute stress. However, the effect of acute stress on learning in advanced parental aged rats remained elusive. This project would explore the hippocampal dependent learning and memory, synaptic transmission and synaptic plasticity in hippocampal CA1, the expression and methylation of relate proteins and DNAs, the concentration of glucocorticoid/estrogen/testosterone in rat of advanced parental age. The interaction of parental age, gender and acute stress on learning and memory would be tested in this project, which could provide some experimental evidence for the prevention and therapy of related mental disorders.