Maternal flu infection and brain development in primates

该项目将使用非人类灵长类动物模型来调查母体流感感染对 婴儿产后行为和大脑功能，建立在许多研究表明怀孕 条件会显著影响胎儿的发育。除了是致病和死亡的原因外， 人们越来越担心，怀孕期间的流感感染可能会导致后代的长期变化，甚至 当产妇的症状看起来是良性的。A/悉尼/5/97控制流感感染的效果 [H3N2]将在108只恒河猴的大队列中进行前瞻性评估。 在比较了孕期和感染严重程度后，第三个实验将确定保护性 在怀孕前三个月接种疫苗的好处，以改善对婴儿的有害影响。这个 所有婴儿的表型和健康状况将以标准化的神经行为和 神经内分泌测试。高分辨率磁共振成像(MRI)技术将用于 检查8个月和12个月大的全球和区域大脑发育情况。脑白质完整性和脑白质损害发生率 髓鞘形成将通过弥散张量成像(DTI)进行评估。这些目标将通过使用 哈洛灵长类实验室和韦斯曼3-Telsa磁共振设施的独特资源 威斯康星州和北卡罗来纳大学的J.Gilmore和G.Gerig博士的分析专业知识。 总体而言，这些研究将检验核心假设，即感染和免疫激活可以改变自然 胎儿发育的进展，表现为新生儿和静止时神经运动反应的异常 影响1岁婴儿的敏感神经过程和行为能力。一个重要的焦点 是海马体的潜在脆弱性及其与 下丘脑-垂体-肾上腺轴。在这个关头，对产前流感感染的灵长类动物的研究至关重要 在啮齿动物模型中的发现和对人类样本的回顾分析提出的关切之间架起了桥梁。

This project will use a nonhuman primate model to investigate the impact of maternal influenza infection on infant behavior and brain functioning postpartum, building upon many studies showing that pregnancy conditions can significantly affect fetal development. In addition to being a cause of morbidity and mortality, concern has grown that flu infections during pregnancy may induce long-term changes in offspring, even when maternal symptoms are seemingly benign. The effect of controlled flu infections with A/Sydney/5/97 [H3N2] in mid- and late- pregnancy will be prospectively assessed in a large cohort of 108 rhesus monkeys. After comparing gestational timing and severity of infection, a third experiment will determine the protective benefits of vaccination in the first trimester for ameliorating the deleterious effects on the baby. The phenotype and wellbeing of all infants will be characterized with standardized neurobehavioral and neuroendocrine tests. High resolution Magnetic Resonance Imaging (MRI) techniques will be employed to examine global and regional brain development at 8 and 12 months of age. White matter integrity and rate of myelinization will evaluated with Diffusion Tensor Imaging (DTI). These aims will be acomplished using the unique resources of the Harlow Primate Laboratory and Waisman 3-Telsa MR facility at the University of Wisconsin and the analytic expertise of Drs. J. Gilmore and G. Gerig at the University of North Carolina. Overall, the studies will test the central hypothesis that infection and immune activation can alter the natural progression of fetal development, be evinced by abnormal neuromotor responses in the neonate and still affect sensitive neural processes and the behavioral competence of the 1 year old infant. An important focus is the potential vulnerability of the hippocampus and its relationship to the regulatory set points of the hypothalamic-pituitary-adrenal axis. Primate studies of prenatal flu infection are critical at this juncture to bridge the findings in rodent models and concerns raised by retrospective analyses of human samples.