Maternal flu infection and brain development in primates

母体流感感染与灵长类动物大脑发育

• 批准号: 7016679
• 负责人: CHRISTOPHER L COE
• 金额: $ 43.41万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-15 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7016679
• 关键词: Macaca mulatta; active immunization; animal developmental psychology; developmental neurobiology; diffusion magnetic resonance imaging; early experience; gestational age; hypothalamic pituitary adrenal axis; infant animal; influenza; influenza vaccines; neuropsychological tests; pregnancy infection; white matter

DESCRIPTION (provided by applicant): 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 accomplished 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.

描述（由申请人提供）：该项目将使用非人灵长类动物模型来研究母体流感感染对婴儿行为和产后大脑功能的影响，建立在许多研究的基础上，这些研究表明妊娠条件可以显着影响胎儿发育。除了是发病和死亡的原因之外，人们越来越担心怀孕期间的流感感染可能会导致后代的长期变化，即使母亲的症状似乎是良性的。将在108只恒河猴的大队列中前瞻性评估A/Sydney/5/97 [H3 N2]在妊娠中期和晚期控制流感感染的影响。在比较妊娠时间和感染的严重程度后，第三个实验将确定在头三个月接种疫苗对改善对婴儿的有害影响的保护作用。所有婴儿的表型和健康状况将通过标准化神经行为和神经内分泌测试进行表征。高分辨率磁共振成像（MRI）技术将用于检查8个月和12个月大时的全球和区域大脑发育。白色物质的完整性和髓鞘化率将通过扩散张量成像（DTI）进行评价。这些目标将利用威斯康星州大学哈洛灵长类动物实验室和韦斯曼3-Telsa MR设施的独特资源以及J. Gilmore和G.北卡罗来纳州大学的格里格。总体而言，这些研究将检验中心假设，即感染和免疫激活可以改变胎儿发育的自然进程，表现为新生儿的异常神经运动反应，并且仍然影响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-肾上腺轴调节设定点的关系。产前流感感染的灵长类动物研究在这个关键时刻至关重要，以弥合啮齿动物模型中的发现和人类样本回顾性分析所引起的担忧。