Biological Consequences of Prenatal Stress and/or Antidep

项目4-摘要 鉴于人类婴儿在子宫内可能暴露于应激源和抗抑郁药物的现实 生活事件的一部分或母亲的适当治疗，长期发育 需要确定对后代的影响，作为长期规划和监测的一个方面 健康问题。该项目侧重于生物后果(生化、分子、生理) 和遗传)与产前应激和宫内抗抑郁药物相互作用的产妇护理质量 这些大鼠成年后对其后代大脑功能的影响 产前暴露于这些因素会改变大脑的长期生物学吗？)这个项目将重点放在三个方面 成人大脑功能的独特方面。1)大脑局部的神经化学和分子变化是什么 这一结果(要检查的标记都是以前公布的，但没有进行测试，将涉及 在应激反应或抗抑郁药物的作用机制中)来自产妇护理、产前应激 暴露，以及在子宫内暴露抗抑郁药物？2)微血管是否有结构变化 向大脑供应血液的系统或信号新血管的血管生成生长因子 队形和后退？例如，尽管CMS的可塑性包括变化，但这是公认的 在突触形态、神经元连接、胶质细胞形态和功能以及 血管系统、产妇护理、早期生活应激源和宫内抗抑郁治疗对 中枢神经只被定位于神经元和神经胶质细胞。3)我们将尝试识别符合以下条件的基因座 受母婴护理质量、产前应激和宫内暴露于 老鼠脑中的抗抑郁药。我们将使用ChlP-on-Chip技术来调查产妇的质量如何 护理、产前应激和宫内暴露于SSRI会改变表观遗传学特征(DNA甲基化 和组蛋白修饰)在出生和成年大鼠大脑中整个基因组的启动子区域。 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洞察 由于母婴护理、产前压力和子宫内的差异而产生的变化或缺乏变化 接触抗抑郁药。

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.