产前应激对子代学习记忆能力损伤的关键机制，是发育中大脑的表观遗传变化。Wnt/β-catenin信号通路参与学习记忆的调控，但未见此通路在孕期慢性应激与子代认知方面的相关研究。我们前期研究发现：孕期应激模型大鼠所产子鼠脑海马神经递质及突触相关蛋白表达较对照组子鼠降低，且与子鼠学习记忆能力下降有正相关性。胚胎早期是子代脑发育的重要时期，本项目拟开展：1）采用iTRAQ蛋白质组学技术鉴定及筛选孕期慢性应激子鼠海马差异蛋白的表达及信号通路。2）通过荧光定量PCR和Western Blot验证Wnt/β-catenin信号通路是否参与孕期慢性应激子鼠海马形成，通过RRBS技术分析此通路相关因子DNA甲基化的CpG岛和DMR差异区域。3）采用枸杞多糖灌胃干预改善孕期慢性应激对其子代学习记忆能力损伤；进而完善孕期慢性应激对子代学习记忆能力损伤机制的理论体系，且可为干预子代认知能力损伤等提供新的思路。

The key mechanism of prenatal stress impairing the learning and memory ability of offspring is epigenetic changes in the developing brain. Wnt/beta-catenin signaling pathway is involved in the regulation of learning and memory, but no related research on the cognitive aspects of offspring under prenatal stress has been found. Previously, our group had found that the learning and memory impairment of offspring induced by chronic stress during pregnancy was related to the changes of central neurotransmitters and the decrease of synaptic-related protein expression in hippocampus. Early embryonic stage is the key period of brain development. This project is to carry out: 1) Differential protein expression in hippocampus of pregnant chronic stress rats was determined using iTRAQ proteomics technology. 2) Quantitative fluorescence PCR and Western Blot were used to verify whether Wnt/β-catenin signaling pathway was involved in hippocampal formation in pregnant chronic stress rats. The difference regions of CpG island and DMR related to DNA methylation in this pathway were analyzed by RRBS technique. 3) Lycium barbarum polysaccharide intervention was used to improve the learning and memory impairment of offspring caused by chronic stress during pregnancy, and then to improve the theoretical system of the mechanism of learning and memory impairment of offspring caused by chronic stress during pregnancy, and to provide new ideas and methods for intervention of cognitive impairment of offspring.