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 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。埃默里孔特精神疾病神经科学中心 - 灵长类动物核心。这项工作的主要目标是在恒河猴中产生和表征非人类灵长类动物表观遗传早期生命应激模型。已经提供了许多程序作为早期压力经历的潜在灵长类动物模型，这些压力经历与成年后焦虑和情感障碍的风险相关。这些范围从长期婴儿隔离模式到短期（1-24 小时）母婴分离然后团聚。前者对社交能力和对压力的敏感性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敏感性的短暂变化，但显然没有长期的行为缺陷。我们对恒河猴在发育的关键时期（3-6 个月大）制定了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的猴子提供早期发育压力。我们研究了母亲反复分离对动物情绪行为和 HPA 轴功能的短期和长期影响。反复与母亲分离会使婴儿变得敏感吗？ HPA 轴对压力的反应，特别是在具有血清素转运蛋白基因 (rh5-HTTLPR) 启动子区域短等位基因的女性和婴儿中。作为青少年，与母亲分离的受试者表现出惊吓反应性增强、皮质醇昼夜节律平坦，以及通过 CRF 和 ACTH 药理学挑战检测到的垂体肾上腺功能的改变。大多数这些改变表明，早期的不良经历导致 CRF 系统和 HPA 轴过度活跃，随后在轴的不同水平发生补偿性下调。负面结果受到性别和血清素转运蛋白基因变异的强烈影响。尽管这些因素之间的相互作用很复杂，但女性和具有短等位基因的受试者更容易受到母亲分离的影响。我们正在纵向跟踪动物，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) 神经成像对大脑血清素功能的研究。