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: 8172310
• 负责人: MAR M SANCHEZ
• 金额: $ 4.39万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172310
• 关键词: Adolescence; Adolescent; Adult; Age-Months; Animal Model; Animals; Anxiety; Behavior; Behavioral; Brain; Brain region; Circadian Rhythms; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Emotional; Exhibits; Female; Funding; Genes; Glucose; Grant; Growth; Hippocampus (Brain); Human; Hydrocortisone; Hyperactive behavior; Immune; Individual; Infant; Institution; Life Stress; Long-Term Effects; Macaca; Measures; Mental disorders; Metabolic; Metabolism; Modality; Monkeys; Neurosciences; Neurosecretory Systems; Physiology; Positron-Emission Tomography; Primates; Proteins; Puberty; Reaction; Recording of previous events; Reporting; Research; Research Personnel; Resources; Sensory; Sensory Process; Serum; Sleep; Sleep disturbances; Social Behavior; Source; Stress; Structure of superior temporal sulcus; System; Testing; Thalamic structure; United States National Institutes of Health; biological adaptation to stress; brain metabolism; critical period; emerging adult; inferotemporal cortex; inflammatory marker; maternal separation; nonhuman primate; putamen; serotonin transporter

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. This project studied the developmental effects of early life stress (ELS) using a nonhuman primate animal model. We have investigated the short- and long-term effects of repeated maternal separation during a critical period of infant macaque development (3-6 months of age). We reported this ELS sensitized the infants' stress responses, particularly in females and infants with low functional serotonin transporter genes. As juveniles, maternally-separated subjects exhibited enhanced anxiety (startle reactivity), flattened cortisol diurnal rhythms and other alterations in stress physiology. During the last year we collected additional longitudinal data of ELS effects on emotional behavior, sleep, physical growth, metabolism, immune and neuroendocrine function during adolescence and adulthood. Findings confirmed enduring effects of the ELS in many of these systems with increased emotional reactivity and problems in social behavior, delayed physical growth around puberty, sleep disturbances and elevated levels of inflammatory markers (e.g. serum c-reactive protein) during adolescence and adulthood. We also examined the long-term effects of the ELS on brain metabolism, using [18F]-fluoro-deoxy-glucose Positron Emission Tomography (FDG-PET) during a mildly stressful test session. Results from these studies showed significantly greater metabolic activity in animals with ELS in brain regions such as superior temporal sulcus, putamen, thalamus, inferotemporal cortex, hippocampus and orbitofrontal cortex, despite no group differences detected in behavioral, autonomic or neuroendocrine measures, suggesting that differences in brain metabolism were not influenced by differential reactions of these systems. These findings suggest that, as adults, monkeys with histories of ELS exhibited hyperactivity in brain regions involved in attending to and regulating sensory information from multiple modalities. Altogether, results suggest that ELS had persistent effects on primates, leading to increased emotional reactivity, alterations in social behavior, homeostatic systems and brain sensory processing during adolescence and early adulthood, which are consistent with features of human psychiatric disorders exhibited by individuals with ELS.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该项目使用非人类灵长类动物模型研究了早期生活压力 (ELS) 对发育的影响。 我们研究了在猕猴幼年发育的关键时期（3-6 个月大）反复与母亲分离的短期和长期影响。我们报告说，这种 ELS 使婴儿的应激反应变得敏感，特别是在女性和具有低功能性血清素转运蛋白基因的婴儿中。作为青少年，与母亲分离的受试者表现出焦虑感增强（惊吓反应性）、皮质醇昼夜节律变平以及应激生理学的其他变化。去年，我们收集了 ELS 对青春期和成年期情绪行为、睡眠、身体生长、新陈代谢、免疫和神经内分泌功能影响的额外纵向数据。 研究结果证实了 ELS 对许多这些系统的持久影响，包括情绪反应性增加和社会行为问题、青春期前后身体生长延迟、睡眠障碍以及青春期和成年期间炎症标志物（例如血清 C 反应蛋白）水平升高。我们还在轻度压力测试期间使用 [18F]-氟脱氧葡萄糖正电子发射断层扫描 (FDG-PET) 检查了 ELS 对大脑代谢的长期影响。这些研究的结果显示，尽管在行为、自主神经或神经内分泌测量方面没有检测到群体差异，但患有ELS的动物的大脑区域（如颞上沟、壳核、丘脑、颞下皮层、海马和眶额皮层）的代谢活动显着增强，这表明大脑代谢的差异不受这些系统的差异反应的影响。这些发现表明，有 ELS 病史的猴子成年后，参与关注和调节来自多种方式的感觉信息的大脑区域表现出过度活跃。 总而言之，结果表明，ELS 对灵长类动物具有持久的影响，导致青春期和成年早期情绪反应性增加、社会行为、稳态系统和大脑感觉处理的改变，这与 ELS 个体表现出的人类精神疾病特征一致。