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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。Emory Conte Center for the Neuroscience of Mental Disorders（英语：Emory Conte Center for the Neuroscience of Mental Disorders）这项工作的主要目标是在恒河猴中产生和表征非人灵长类表观遗传早期生活应激模型。许多程序已被提供作为潜在的灵长类动物模型的早期压力的经验与随后的风险，焦虑和情感障碍的成年。这些模式从长期的婴儿隔离模式到短期（1-24小时）母婴分离，然后团聚。前者几乎会永久性地破坏社会能力和对压力的敏感性。后者产生社会行为的急剧变化和对压力敏感性的短暂变化，但显然没有长期的行为缺陷。我们在恒河猴发育的关键时期（3-6个月大）实施了一个重复母婴分离的时间表。该项目的目的是为埃默里精神障碍神经科学中心提供早期发育压力的猴子。我们研究了反复的母亲分离对动物情绪行为和HPA轴功能的短期和长期影响。反复的母婴分离会使婴儿过敏吗？HPA轴对应激的反应，特别是在女性和婴儿中具有5-羟色胺转运体基因（rh 5-HTTLPR）启动子区的短等位基因。作为青少年，母亲分离的主题表现出增强惊吓反应，平坦的皮质醇昼夜节律和垂体肾上腺功能的变化与CRF和ACTH药理学挑战检测。大多数这些变化表明，早期的不良经历引起CRF系统和HPA轴的过度活跃，随后在轴的不同水平代偿性下调。性别和5-羟色胺转运体基因变异对阴性结果有很大影响。虽然这些因素之间的相互作用是复杂的，女性和主题的短等位基因更容易受到影响的孕产妇分离。我们正在纵向跟踪这些动物，包括目前对生长、代谢和免疫功能的研究，以及使用正电子发射断层扫描（PET）神经成像技术对脑多巴胺能功能的研究。