发生于人类生命早期的不良生活事件会增加个体成年后躯体疾病和精神障碍的风险，因此，研究生命早期不良生活经历（应激）如何影响成年个体的身心健康是精神医学中一项重要的课题。NAP是一段由8个氨基酸构成的高效神经保护肽，然而人工合成的NAP成本高，在水溶液中稳定性差，在体内半衰期短，极易降解，更由于其基因序列缺少分泌表达元件而常常滞留于细胞不能发挥生物活性，这些局限性严重制约着NAP实际应用于CNS疾病的治疗。本课题拟采用母婴分离（MS）和社会隔离（SI）两种最常使用的动物模型研究生命早期应激的神经可塑性机制，并尝试利用基因工程技术将NAP与神经营养素4（NT4）的信号肽与前导序列连接，构建融合基因 NT4-NAP，使原核分泌表达的融合基因具有良好的生物学活性，再经鼻途径给药，使之可用于干预MS、SI模型。上述策略和方法为神经保护肽的实际临床应用提供了良好的范本。

In humans, environmental adversity occurring in early life is associated with an increased risk of both physical and psychiatric disorder in adulthood. Therefore, it is important in psychiatry to study how early environmental effects sustained into adulthood. NAP (generic name davunetide) is a neuroprotective peptide consisting of eight amino acids (NAPVSIPQ) derived from activity-dependent neuroprotective protein (ADNP). However, synthetic NAP is expensive, instable in aqueous solutions, shorter half-life in vivo, easily degradable and usually unable to have biological activity arrested in the cells because of lacking of secretion and expression elements in the sequence. All these limitations severely restricted the NAP practical application in the therapy of CNS diseases. Therefore, in this present proposal, we try to investigate effects of early life stress on neuroplasticity by using two animal models, which are maternal separation (MS) model and social isolation (SI) model. Furthermore, we plan to fuse the signal peptide of neurotrophin 4 (NT4) to NAP to generate NT4-NAP, and we propose that the fusion peptide will show a good biological activity in the intervention of MS and IS by intranasal route. We hope this study will provide a reliable strategy for neuroprotective peptide in the clinical trials on neuroplasticity disease.