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

项目总结/摘要 对压力的敏感性增加会导致适应不良的应对行为，如社交退缩和 侵略经历早期生活逆境（ELA）的儿童患上类似疾病的风险增加。 困难，特别是在以后的生活中经历了压力事件之后。父母的照顾， 特别是护理，可以对社会行为和福祉的发展产生保护作用。然而 父亲的照顾和神经内分泌因素的影响，参与对晚年生活压力的反应， 后代的研究还远远不够，哺乳动物双亲照顾和压力的动物模型 非常需要作出反应。此外，催产素（OT）和加压素（VP）是必需的神经肽， 调节社会行为，但其受体基因的表观遗传修饰对ELA的反应还没有被证实。 很好的描述。我将通过使用双亲大草原开发一个ELA和青少年压力的两次打击模型 田鼠（Microtus ochrogaster），以评估在特定的断奶前敏感窗口期间父系剥夺 通过OT和VP相关的横向变化对青少年慢性社会失败压力的偏见敏感性 隔膜和其中的神经活动。在草原田鼠的后代中，从出生开始就剥夺父系的影响， 据报道，诱导缺陷的配对键，区域特异性和性别特异性的修改OT和VP 受体表达然而，在研究破坏直接父亲关系的后果方面存在研究空白。 照顾或打破父子关系，父亲剥夺与慢性社会失败压力的相互作用， 及其对介导后代社会行为的遗传、表观遗传、转录组机制的集体影响 和大脑发育。该项目将整合多个层次的分析（行为，表观遗传，细胞特异性 基因和蛋白质分析，以及神经元功能），以了解侧隔的机制， 父亲的剥夺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.