Biological Consequences of Prenatal Stress and/or Antidep

产前应激和/或 Antidep 的生物学后果

• 批准号: 7931869
• 负责人: MICHAEL JOSEPH OWENS
• 金额: $ 34.14万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7931869
• 关键词: Address; Adult; Age; Antidepressive Agents; Arts; Behavior; Biochemical; Biochemical Markers; Biological; Biology; Birth; Blood Vessels; Brain; Brain region; Caring; DNA Methylation; Development; Epigenetic Process; Event; Exposure to; Genes; Genetic; Genome; Growth Factor; Health; Human; Infant; Life; Measures; Medical; Molecular; Molecular Profiling; Monitor; Morphology; Mothers; Neuraxis; Neurobiology; Neuroglia; Neurons; Pathway interactions; Perinatal; Perinatal Exposure; Physiological; Promoter Regions; Rattus; Selective Serotonin Reuptake Inhibitor; Signal Transduction; Stress; Synapses; System; Techniques; Technology; Testing; Vascular blood supply; abstracting; histone modification; in utero; insight; mRNA Expression; maternal stress; neurochemistry; offspring; prenatal exposure; prenatal stress; reproductive; stressor

PROJECT 4 - Abstract Given the reality that human infants can be exposed to stressors and antidepressant drugs in utero as part of life events or appropriate medical treatment of the mother, the long term developmental consequences on the offspring need to be determined as one aspect of planning and monitoring long term health issues. This project focuses upon the biological consequences (biochemical, molecular, physiological and genetic) of the quality of maternal care interacting with prenatal stress and in utero antidepressant exposure on brain function of offspring when these rats become adults of reproductive age (i.e., does prenatal exposure to these factors alter the long term biology of the brain?). This project will focus on three unique aspects of adult brain function. 1) What are the regional brain neurochemical and molecular changes that result (the markers to be examined have all been previously promulgated, but not tested, to be involved in stress responsivity or the mechanisms of action of antidepressants) from maternal care, prenatal stress exposure, and in utero antidepressant exposure? 2) Are there structural changes in the microvascular system supplying blood to the brain or in the angiogenic growth factors that signal new blood vessel formation and retraction? For example, although.it is well established that CMS plasticity includes changes in synaptic morphology, neuronal connectivity, glial morphology and function as well as changes in vasculature, the effects of maternal care, early life stressors, and in utero antidepressant treatment on the CNS have only been addressed for neurons and glia. 3) We will attempt to identify genetic loci that are epigenetically altered by the quality of maternal care, prenatal stress, and in utero exposure to antidepressants in rat brains. We will use ChlP-on-chip technology to investigate how the quality of maternal care, prenatal stress, and in utero exposure to SSRI's alter the epigenetic profiles (both DNA methylation and histone modification) of the promoter regions across the genome in rat brains at birth and in adulthood. In addition, the mRNA expression profiles from the same brain regions will be evaluated and correlated with the epigenetic profiles. These state-of-the-art techniques can offer unique insight into the long term changes, or lack thereof, produced by differences in maternal care, prenatal stress, and in utero antidepressant exposure.

项目4 -摘要 考虑到人类婴儿在子宫内可能暴露于压力源和抗抑郁药物的现实， 部分生活事件或母亲的适当医疗， 作为长期规划和监测的一个方面，需要确定对后代的影响 健康问题。该项目的重点是生物后果（生物化学，分子，生理 和遗传）的质量与产前压力和子宫内抗抑郁药相互作用的孕产妇保健 当这些大鼠成为育龄成年大鼠时，并 产前暴露于这些因素会改变大脑的长期生物学？）该项目将重点关注三个 成人大脑功能的独特方面1)什么是局部脑神经化学和分子变化 这一结果（要检查的标记都是以前公布的，但没有测试，将涉及 在压力反应或抗抑郁药的作用机制）从产妇护理，产前压力 暴露和子宫内抗抑郁药暴露2)微血管是否有结构变化 系统供应血液到大脑或在血管生成生长因子的信号新的血管 形成和收缩？例如，although.it已经很好地确立了CMS可塑性包括改变 在突触形态学、神经元连接性、神经胶质形态和功能以及 血管，孕产妇护理，早期生活压力源和子宫内抗抑郁药治疗对 CNS仅涉及神经元和神经胶质。3)我们将尝试找出遗传位点， 表观遗传改变的质量，孕产妇保健，产前压力，并在子宫内暴露于 抗抑郁药的作用我们将使用ChIP芯片技术来研究如何提高孕产妇的质量， 护理、产前压力和子宫内暴露于SSRI会改变表观遗传特征（DNA甲基化 和组蛋白修饰）在出生时和成年时大鼠脑中基因组的启动子区域。 此外，将评估来自相同脑区域的mRNA表达谱，并将其与 表观遗传特征这些最先进的技术可以提供独特的洞察力， 变化，或缺乏，由不同的产妇护理，产前压力，并在子宫内产生的 抗抑郁药暴露