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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究以非人类灵长类动物为研究对象，探讨早期生活压力（ELS）对发育的影响。 我们已经调查了短期和长期的影响，反复母亲分离期间的关键时期的婴儿猕猴发展（3-6个月的年龄）。我们报道了ELS致敏婴儿的应激反应，特别是在女性和低功能5-羟色胺转运体基因的婴儿中。作为青少年，母亲分离的受试者表现出增强的焦虑（惊吓反应），平坦的皮质醇昼夜节律和其他压力生理学的变化。在过去的一年中，我们收集了额外的纵向数据ELS对青少年和成年期的情绪行为，睡眠，身体发育，新陈代谢，免疫和神经内分泌功能的影响。 研究结果证实了ELS在许多这些系统中的持久影响，其中包括情绪反应性增加和社会行为问题，青春期周围的身体发育延迟，青春期和成年期的睡眠障碍和炎症标志物（例如血清C反应蛋白）水平升高。我们还研究了ELS对大脑代谢的长期影响，在轻度压力测试期间使用[18 F]-氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）。这些研究的结果表明，尽管在行为、自主神经或神经内分泌测量中没有检测到组间差异，但在具有ELS的动物中，大脑区域（如上级颞沟、壳核、丘脑、颞下皮质、海马和眶额皮质）的代谢活性显著更高，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，成年后，有ELS病史的猴子在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。 总之，研究结果表明，ELS对灵长类动物有持续的影响，导致情绪反应性增加，在青春期和成年早期的社会行为，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的特征一致。