Maternal flu infection and brain development in primates

该项目将使用非人灵长类动物模型来研究母亲感染流感对 婴儿的行为和产后大脑功能，建立在许多研究表明，怀孕， 会严重影响胎儿的发育除了是发病和死亡的原因之外， 人们越来越担心，怀孕期间感染流感可能会导致后代的长期变化， 母亲的症状看似良性用A/Sydney/5/97控制流感感染的效果 [H3 N2]在妊娠中期和晚期的发病率将在108只恒河猴的大型队列中进行前瞻性评估。 在比较了妊娠时间和感染的严重程度后，第三个实验将确定保护性 在怀孕的头三个月接种疫苗的好处，以减轻对婴儿的有害影响。的 所有婴儿的表型和健康将以标准化的神经行为和 神经内分泌测试将采用高分辨率磁共振成像（MRI）技术， 检查8个月和12个月大时的整体和区域大脑发育。白色物质完整性和 将用扩散张量成像（DTI）评价髓鞘化。这些目标将通过使用 哈洛灵长类动物实验室和韦斯曼3-Telsa MR设施的独特资源， 威斯康星州和分析专业知识的博士。北卡罗来纳州大学的格里格。 总的来说，这些研究将测试中心假设，即感染和免疫激活可以改变自然 胎儿发育的进展，可以通过新生儿的异常神经运动反应来证明， 影响敏感的神经过程和1岁婴儿的行为能力。一个重要焦点 是海马体的潜在脆弱性及其与大脑皮层的调节设定点的关系。 下丘脑垂体肾上腺轴在这个关键时刻，对产前流感感染的灵长类动物研究至关重要， 将啮齿动物模型中的发现与对人类样本的回顾性分析所引起的担忧联系起来。

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.