EPIGENETIC RISK FOLLOWING EARLY LIFE STRESS IN INFANT RHESUS MACAQUES

幼年恒河猴早期生活压力带来的表观遗传风险

• 批准号: 8357356
• 负责人: Erin Loraine Kinnally
• 金额: $ 5.04万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357356
• 关键词: Antidepressive Agents; California; Depressed mood; Enhancers; Epigenetic Process; Funding; Glucocorticoid Receptor; Grant; Individual; Infant; Intervention; Life; Life Stress; Macaca mulatta; Mediating; Mental Health; NR3C1 gene; National Center for Research Resources; Neural Pathways; Patients; Primates; Principal Investigator; Psychopathology; Research; Research Infrastructure; Resources; Risk; Source; Stress; Trauma; United States National Institutes of Health; cost; early experience; gene function; improved; relating to nervous system; serotonin transporter; stressor; transcription factor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The experience of early life stress puts individuals at greater risk for psychopathology later in life. Multiple neural pathways contribute to this risk, but the serotonin transporter (5-HTT) is among the foremost of these. The target of the most effective antidepressants, neural 5-HTT expression is lower in depressed patients and in victims of early life stress. Identifying the mechanism(s) of plasticity in 5-HTT gene function or of its transcription factors following early stress may therefore inform intervention strategies to improve mental health following trauma. The PI will investigate whether a well-characterized experimental early life stressor leads to dysregulation of 5-HTT and one of its major transcriptional enhancers(glucocorticoid receptor, NR3C1 or GR) in infant rhesus macaques, and whether this dysregulation is epigenetically mediated.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 早期生活压力的经历使个人在以后的生活中面临更大的精神病理风险。多种神经通路导致这种风险，但5-羟色胺转运体(5-HTT)是其中最重要的。作为最有效的抗抑郁药物的靶标，神经性5-HTT在抑郁症患者和早期生活压力的受害者中的表达较低。因此，确定早期应激后5-HTT基因功能或其转录因子可塑性的机制(S)可能会为改善创伤后心理健康的干预策略提供参考。PI将调查一种具有良好特征的实验性早期生活应激源是否导致婴儿恒河猴5-HTT及其主要转录增强子之一(糖皮质激素受体，NR3C1或GR)的失调，以及这种失调是否由表观遗传介导。