EPIGENETIC RISK FOLLOWING EARLY LIFE STRESS IN INFANT RHESUS MACAQUES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 早期生活压力的经历使个体在以后的生活中面临更大的精神病理学风险。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。最有效的抗抑郁药的目标，神经5-HTT表达在抑郁症患者和早期生活压力的受害者中较低。因此，确定5-HTT基因功能或其转录因子在早期应激后的可塑性机制可能为改善创伤后心理健康的干预策略提供信息。PI将研究一种充分表征的实验性早期生活应激源是否导致幼年恒河猴中5-HTT及其主要转录增强子之一（糖皮质激素受体，NR 3C 1或GR）的失调，以及这种失调是否由表观遗传学介导。

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.