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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目使用非人类灵长类动物模型研究了早期生命应力（EL）的发育效果。 我们已经调查了在婴儿猕猴发育的关键时期（3-6个月大）重复产妇分离的短期和长期影响。我们报道了ELS对婴儿的压力反应敏感，特别是在功能低下的5-羟色胺转运蛋白基因的婴儿中。作为少年，母亲分离的受试者表现出增强的焦虑（惊吓反应性），皮质醇昼夜节奏的扁平性和压力生理学的其他改变。在过去的一年中，我们收集了ELS对情绪行为，睡眠，身体生长，代谢，免疫和神经内分泌功能的其他纵向数据。 研究结果证实了EL在许多系统中的持久影响，情绪反应性和社交行为的问题增加，青春期障碍和炎症标记水平升高（例如，青春期和成年期）的炎症标志物（例如血清C反应蛋白）的水平升高。我们还使用[18F] - 氟 - 脱氧 - 葡萄糖正电子发射断层扫描（FDG-PET）研究了EL对脑代谢的长期影响。这些研究的结果表明，尽管在行为，自主性或神经内分泌措施中未发现群体差异，但在脑部差异上没有差异，但在行为，自主神经或神经内分泌措施中未发现群体差异，但在脑部差异上没有发现这些差异，诸如脑部的差异差异。这些发现表明，作为成年人，具有EL历史的猴子在参与参与和调节多种方式的感官信息的大脑区域表现出多动症。 总而言之，结果表明，ELS对灵长类动物有持续的影响，导致情绪反应性的增加，社会行为的改变，体内稳态系统以及青春期和成年初期的大脑感觉处理，这与人类精神疾病的特征是一致的。