Biological Consequences of Prenatal Stress and/or Antidep

产前应激和/或 Antidep 的生物学后果

• 批准号: 8111196
• 负责人: MICHAEL JOSEPH OWENS
• 金额: $ 33.89万
• 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: 2010-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8111196
• 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; Genetic; Genome; Growth Factor; Health; Human; Infant; Life; Measures; Medical; Molecular; Molecular Profiling; Monitor; Morphology; Mothers; Neuraxis; Neurobiology; Neuroglia; Neurons; 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 鉴于人类婴儿可能​​在子宫内暴露于压力源和抗抑郁药物的现实 母亲生活事件或适当医疗的一部分，长期发展 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。该项目重点关注生物学后果（生化、分子、生理学） 孕产妇护理质量与产前压力和子宫内抗抑郁药物的相互作用 当这些老鼠成年后，后代的大脑功能会受到影响（即， 产前接触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) 大脑区域神经化学和分子变化有哪些 该结果（待检查的标记均已颁布，但未测试，涉及 压力反应或抗抑郁药的作用机制）来自产妇护理、产前压力 暴露和子宫内抗抑郁药暴露？ 2）微血管结构是否发生变化？ 向大脑供血的系统或发出新血管信号的血管生成生长因子 形成和收缩？例如，尽管 CMS 可塑性包括变化，这一点已得到充分证实 突触形态、神经元连接、神经胶质形态和功能以及 脉管系统、孕产妇护理、早期生活压力源和子宫内抗抑郁治疗对 中枢神经系统仅针对神经元和神经胶质细胞。 3）我们将尝试识别以下基因位点： 孕产妇护理质量、产前压力和子宫内暴露会导致表观遗传改变 大鼠大脑中的抗抑郁药。我们将使用 ChlP-on-chip 技术来研究母体质量如何 护理、产前应激和子宫内暴露于 SSRI 会改变表观遗传特征（DNA 甲基化 和组蛋白修饰）对出生和成年大鼠大脑中基因组的启动子区域进行研究。 此外，来自相同大脑区域的 mRNA 表达谱将被评估并与 表观遗传特征。这些最先进的技术可以提供对长期的独特见解 由于产妇护理、产前压力和子宫内的差异而产生的变化或缺乏 抗抑郁药暴露。