EMORY CONTE CENTER FOR THE NEUROSCIENCE OF MENTAL DISORDERS: PRIMATE CORE

埃默里孔特精神障碍神经科学中心：灵长类核心

• 批准号: 7349141
• 负责人: MAR SANCHEZ
• 金额: $ 4.01万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-09 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349141
• 关键词: Primates; alleles; experience; female; genes; model; parents; serotonin transporter; stress

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Emory Conte Center for the Neuroscience of Mental Disorders - Primate Core. The major goal of this work is to produce and characterize a non-human primate epigenetic early life stress model in rhesus monkeys. A number of procedures have been offered as potential primate models of early stress experience associated with subsequent risk for anxiety and affective disorders in adulthood. These range from the chronic infant isolation paradigms to short-term (1-24 hr) mother-infant separations followed by reunion. The former produce near-permanent disruptions in social competence and sensitivity to stress. The latter produce acute changes in social behavior and transient changes in sensitivity to stress, but apparently no long-term behavioral deficits. We have imposed a schedule of repeated mother-infant separations in rhesus macaques during a critical period of development (3-6 months of age). The purpose of this project is to provide monkeys with an early developmental stress to the Emory Center for the Neuroscience of Mental Disorders. We have investigated the short-term and long-term effects of repeated maternal separation on emotional behavior and HPA axis function of the animals. Repeated maternal separation sensitized the infants? HPA axis responses to stress, particularly in females and infants with the short allele of the promoter region of the serotonin transporter gene (rh5-HTTLPR). As juveniles, maternally-separated subjects exhibited enhanced startle reactivity, flattened cortisol diurnal rhythms and alterations in pituitary-adrenal function detected with CRF and ACTH pharmacological challenges. Most of these alterations suggest that the early adverse experience caused hyperactivity of CRF systems and HPA axis, followed by a subsequent compensatory downregulation at different levels of the axis. The negative outcomes were strongly affected by sex and serotonin transporter gene variation. Although the interactions between these factors are complex, females and subjects with the short allele were more vulnerable to the effects of maternal separations. We are following the animals longitudinally, including current studies of growth, metabolism and immune function, as well as of brain serotonergic function using positron emission tomography (PET) neuroimaging.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。埃默里·孔特精神疾病神经科学中心-灵长类核心。这项工作的主要目标是在恒河猴身上建立和表征一种非人类灵长类动物表观遗传早期生活应激模型。作为早期应激体验与成年后焦虑和情感障碍风险相关的潜在灵长类动物模型，已经提供了一些程序。从长期的婴儿隔离模式到短期(1-24小时)母婴分离，再到随后的团聚。前者会在社交能力和对压力的敏感性方面造成近乎永久性的破坏。后者会导致社会行为的急剧变化和对压力的敏感性的短暂变化，但显然不会造成长期的行为缺陷。我们对恒河猴在发育的关键时期(3-6个月大)实施了反复母婴分离的时间表。该项目的目的是为埃默里精神疾病神经科学中心的猴子提供早期发育应激。我们研究了反复母体分离对动物情绪行为和HPA轴功能的短期和长期影响。反复的母体分离使婴儿变得敏感？HPA轴对压力做出反应，特别是在女性和具有5-羟色胺转运体基因启动子区短等位基因(RH5-HTTLPR)的婴儿中。在青少年时期，母亲分离的受试者表现出惊吓反应增强，皮质醇昼夜节律平坦，以及在CRF和ACTH药理学挑战中检测到的垂体-肾上腺功能的变化。这些改变大多表明，早期的不良经历导致CRF系统和HPA轴的过度活动，随后轴的不同水平出现代偿性下调。性别和5-羟色胺转运体基因变异对阴性结果有很大影响。尽管这些因素之间的相互作用很复杂，但女性和携带短等位基因的受试者更容易受到母体分离的影响。我们正在对动物进行纵向跟踪，包括目前对生长、新陈代谢和免疫功能的研究，以及使用正电子发射断层扫描(PET)神经成像对大脑5-羟色胺能功能的研究。