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

父亲照顾对压力应对行为和神经肽系统的影响

• 批准号: 10580597
• 负责人: Lindsay L Sailer
• 金额: $ 7.38万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580597
• 关键词: 3' Untranslated Regions; AVPR1A gene; Acceleration; Adolescence; Adolescent; Adult; Age; Aggressive behavior; Animal Model; Behavioral; Biological Markers; Birth; Brain; Buffers; Caring; Cells; Child; Chronic; Code; Communication; Complex; Coping Behavior; DNA Methylation; Development; Elderly; Epigenetic Process; Exhibits; FOS Protein; Fathers; Female; Fright; Gene Expression; Genes; Genetic; Genetic Transcription; Individual; Lateral; Life; Life Stress; Measures; Mediating; Mental Depression; Mental disorders; Messenger RNA; Methylation; Microtus; Modeling; Modification; Mus; Neurobiology; Neurons; Neuropeptides; Neurosecretory Systems; Output; Oxytocin; Oxytocin Receptor; Pair Bond; Parent-Child Relations; Paternal Deprivation; Personal Satisfaction; Phenotype; Population; Predisposition; Process; Promoter Regions; RNA; Receptor Gene; Reporting; Research; Risk; Rodent; Role; Sex Differences; Social Behavior; Social Development; Stress; Stress and Coping; Stressful Event; System; Testing; Transcriptional Regulation; Translating; Untranslated RNA; Vasopressin Receptor; Vasopressins; Weaning; Withdrawal; Work; antagonist; avoidance behavior; behavioral phenotyping; biological adaptation to stress; brain behavior; coping; designer receptors exclusively activated by designer drugs; differential expression; early experience; early life adversity; epigenetic regulation; experience; experimental study; gene function; gene repression; insight; mRNA Expression; male; neglect; neural; neuropsychiatric disorder; neuroregulation; novel; novel therapeutic intervention; offspring; prairie vole; promoter; protective effect; protein profiling; receptor expression; response; sex; skills; social; social defeat; social stress; stress resilience; stressor; transcriptomics

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.

项目概要/摘要 对压力的高度敏感可能导致适应不良的应对行为，例如社交退缩和 侵略。经历过生命早期逆境（ELA）的儿童出现类似经历的风险会增加 困难，特别是在以后的生活中经历了随后的压力事件之后。父母的照顾和父亲的照顾 尤其是护理，可以对社会行为和福祉的发展产生保护作用。然而， 父亲照顾的影响以及参与晚年压力反应的神经内分泌因素 后代的研究还远远不够，并且是哺乳动物双亲照顾和压力的动物模型 非常需要反应能力。此外，催产素 (OT) 和加压素 (VP) 是重要的神经肽， 调节社会行为，但其受体基因响应 ELA 的表观遗传修饰尚未被研究 特征良好。我将利用双亲草原开发 ELA 和青少年压力的双重打击模型 田鼠（田鼠）评估特定断奶前敏感窗口期间父本剥夺的情况 通过 OT 和 VP 相关的横向变化，使对青少年慢性社交失败压力的敏感性产生偏差 隔膜和其中的神经活动。父亲剥夺出生对草原田鼠后代的影响 据报道会导致配对缺陷，以及 OT 和 VP 的区域特异性和性别特异性修饰 受体表达。然而，在检验破坏直接父系关系的后果方面存在研究空白。 照顾或破坏父子关系、父亲剥夺与长期社会挫败压力的相互作用、 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面的分析（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）通过以下方式了解外侧隔膜的机制 父亲的剥夺可以减轻青春期对压力源的反应。