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: 7715673
• 负责人: MAR M SANCHEZ
• 金额: $ 2.85万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715673
• 关键词: Adolescence; Adolescent; Adrenal Glands; Age; Age-Months; Alleles; Animals; Behavior; Body Weight; Circadian Rhythms; Computer Retrieval of Information on Scientific Projects Database; Corticotropin; Data; Dental crowns; Development; Emotional; Endocrine; Epigenetic Process; Exhibits; Fasting; Fatty acid glycerol esters; Female; Funding; Genes; Glucose; Goals; Grant; Growth; HPSE gene; Heel; Height; Hydrocortisone; Infant; Institution; Insulin; Length; Leptin; Life Stress; Lipids; Long-Term Effects; Macaca mulatta; Measures; Mental disorders; Metabolic; Metabolic syndrome; Metabolism; Modeling; Monkeys; Mothers; Neurosciences; Phenotype; Pituitary Gland; Plasma; Polysomnography; Primates; Promoter Regions; Puberty; Purpose; Rate; Reporting; Research; Research Personnel; Resources; Sampling; Schedule; Serum; Sleep; Sleep Fragmentations; Sleep disturbances; Social Behavior; Somatotropin; Source; Stress; Time; United States National Institutes of Health; actigraphy; base; bone; critical developmental period; ghrelin; hypothalamic-pituitary-adrenal axis; maternal separation; monoamine; nonhuman primate; response; 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. Emory Conte Center for the Neuroscience of Mental Disorders - Primate Core. The major goal of this project has been to produce and characterize a non-human primate epigenetic early life stress model in rhesus monkeys. 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 the Primate Core is to provide, maintain and characterize phenotypes of monkeys with an early developmental stress for 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. We previously reported that repeated maternal separations 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. Last year we collected more data for longitudinal analyses of: (a) HPA and HPT axes function at later ages (juvenile-adolescence-early adulthood periods), and detected sensitized cortisol responses to stress after habituation paradigms; (b) CSF levels of monoamine metabolites and CRF; (c) Physical growth and metabolism: every 6 months we collected measures of height (crown-rump, crown-heel length), body weight, BMI, bone maturity (rated from radiographs), as well as plasma samples for measures of growth hormone, leptin, ghrelin, etc; so far we have detected delayed physical growth and maturation around puberty, in parallel with increased BMI and fat mass, in maternally-separated monkeys that need to be compared with additional metabolic measures (such as fasting serum glucose, insulin, leptin, and lipid levels to define levels of metabolic syndrome caused by the early life stress); (d) Sleep and activity: using activity-based sleep monitoring (actigraphy) we have detected sleep disturbances in the maternally separated animals during adolescence (less time asleep, reduced sleep efficiency, more sleep fragmentation, higher activity during the night); (e) Social behavior. These recent findings suggest that early life stress has persistent effects on nonhuman primates, leading to alterations in endocrine function, delayed physical growth and maturation, and alterations in sleep and metabolism in peri-pubertal and adolescent monkeys.

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。 Emory Conte Center for the Neuroscience of Mental Disorders（英语：Emory Conte Center for the Neuroscience of Mental Disorders） 该项目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。 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。灵长类核心的目的是为埃默里精神障碍神经科学中心提供、维持和表征具有早期发育应激的猴子的表型。 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。我们以前曾报道，反复的母亲分离敏感的婴儿的HPA轴反应的压力，特别是在女性和婴儿的5-羟色胺转运蛋白基因（rh 5-HTTLPR）的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。去年，我们收集了更多的数据进行纵向分析：（a）HPA和HPT轴功能在以后的年龄（青少年-青春期-成年早期），并检测习惯化范例后对应激的致敏皮质醇反应;（B）单胺代谢物和CRF的CSF水平;（c）身体生长和代谢：每6个月我们收集一次身高数据（顶臀、顶踵长度）、体重、BMI、骨成熟度（根据放射照片评级），以及用于测量生长激素、瘦素、胃饥饿素等的血浆样品;到目前为止，我们已经检测到青春期前后身体发育和成熟的延迟，与BMI和脂肪量的增加平行，需要与额外的代谢测量进行比较，（如空腹血清葡萄糖、胰岛素、瘦素和脂质水平，以定义由早期生活压力引起的代谢综合征的水平）;（d）睡眠和活动：使用基于活动的睡眠监测（活动记录法），我们已经检测到在青春期期间与母亲分离的动物的睡眠障碍（睡眠时间更少，睡眠效率降低，睡眠碎片更多，夜间活动更高）;（e）社会行为。这些最近的研究结果表明，早期生活压力对非人灵长类动物有持续的影响，导致内分泌功能的改变，身体生长和成熟延迟，以及青春期和青春期猴睡眠和代谢的改变。