Impact of paternal care on stress-coping behaviors and neuropeptide systems

项目摘要/摘要 对压力的高度敏感会导致不适应的应对行为，如社交退缩和 攻击性。经历早期生活逆境(ELA)的儿童患类似疾病的风险增加 困难，特别是在经历了后来生活中的压力事件之后。父母的关怀，父亲的关怀 特别是关爱，可以对社会行为的发展和福祉起到保护作用。然而， 父性关怀和神经内分泌因素对老年人晚年生活应激反应的影响 后代的研究还很少，是哺乳动物双亲照料和压力的动物模型 非常需要响应性。此外，催产素(OT)和加压素(VP)是必需的神经肽， 调节社会行为，但它们的受体基因对ELA的表观遗传修饰尚未得到 很好的特点。我将利用双亲草原建立一个两次成功的ELA和青少年压力模型 田鼠(Microtus Ochrogaster)评估父亲在特定的断奶前敏感窗口中的剥夺 通过OT和VP相关的侧脑变化使青少年对慢性社会失败压力的敏感性发生偏差 隔膜和其中的神经活动。草原田鼠后代从出生起就被剥夺父权的影响 已报道导致配对结合缺陷，以及OT和VP中特定区域和特定性别的修饰 受体表达。然而，在研究扰乱直接父系关系的后果方面存在研究空白。 照顾或打破父子关系，父亲的剥夺与长期的社会失败压力的相互作用， 及其对遗传、表观遗传、转录机制的集体影响 和大脑发育。该项目将整合多个层次的分析(行为、表观遗传学、细胞特异性 基因和蛋白质图谱，以及神经元功能)，以了解外侧隔的机制 剥夺父亲的权利可以减轻青春期对压力源的反应。

Project Summary/Abstract Heightened sensitivity to stress can lead to maladaptive coping behaviors, such as social withdrawal and aggression. Children that experience early-life adversity (ELA) have an increased risk of developing similar difficulties, particularly after experiencing subsequent stressful events in later life. Parental care, and paternal care in particular, can have protective effects on the development of social behavior and well-being. Yet, the impact of paternal care and the neuroendocrine factors that are involved in responsiveness to later life stress in offspring are vastly understudied, and an animal model for mammalian biparental care and stress responsiveness is greatly needed. Further, oxytocin (OT) and vasopressin (VP) are essential neuropeptides that modulate social behaviors but epigenetic modifications of their receptor genes in response to ELA have not been well characterized. I will develop a two-hit model of ELA and adolescent stress by using the bi-parental prairie vole (Microtus ochrogaster) to assess how paternal deprivation during a specific pre-weaning sensitive window biases sensitivity to adolescent chronic social defeat stress through OT- and VP-related changes in the lateral septum and neural activity therein. The effects of paternal deprivation from birth in prairie vole offspring have been reported to induce deficits in pair bonding, and region-specific and sex-specific modifications in OT and VP receptor expression. Yet there is a research gap in examining the consequences of disrupting direct paternal care or breaking father-offspring bonds, the interaction of paternal deprivation with chronic social defeat stress, and its collective impact on genetic, epigenetic, transcriptomic mechanisms the mediate offspring social behavior and brain development. This project will integrate multiple levels of analysis (behavioral, epigenetic, cell-specific gene and protein profiling, and neuronal function) to understand the mechanisms in the lateral septum through which paternal deprivation can mitigate reactivity to stressors in adolescence.