Effects of Prenatal Nutrition on Developmental Outcomes in the the Juvenile Baboo

描述（由申请方提供）：拟定研究利用R21探索性/发育研究资助计划探索限制性产前营养对幼年狒狒认知和行为/情感功能的影响。重要性：怀孕和哺乳期间的营养不良与人类后代的负面结果有关，包括认知缺陷以及行为和情感问题。这些发现对儿童健康的影响非常重要，但很难确定营养不足是否真的会导致人类的不良后果。一个随机分配营养水平的非人灵长类动物模型可以建立因果关系，这反过来又会导致关于怀孕期间营养缺乏影响胎儿的机制的可检验的假设。此外，还需要数据来确定后代面临的风险是否会受到怀孕期间因素或产后护理环境的影响。方法：我们将前瞻性地研究狒狒的后代，这些狒狒被随机分配到中度营养限制（即，母亲进食量比随意喂养的母亲少30%）或在妊娠期和哺乳期随意喂养。将在20个月大（相当于人类6岁）时，在神经心理成套测验（剑桥神经心理自动成套测验）的背景下评估青少年的认知和行为/情感功能。此外，我们将测试是否在怀孕期间的营养限制和发育结果之间的关联是由母亲的优势地位或产后护理的缓和。拟议的研究与R21机制一致，原因有二：第一，该模型，包括认知和行为/情绪调节的依赖性测量，是新的和探索性的;第二，该研究是开发更广泛的研究计划的必要的第一步，该计划涉及妊娠期间营养影响发育中的大脑的机制。工作环境：该项目结合了德克萨斯大学圣安东尼奥分校、德克萨斯大学圣安东尼奥分校健康科学中心和芝加哥大学的研究人员的技能。该合作源于NIMH翻译科学网络。Bartlett博士有15年的圈养和野生非人灵长类动物工作经验。巴特利特博士和尼兰德博士合作了三年，收集了群居狒狒的社会行为数据。Keenan博士的研究重点是与儿童早期精神病理学发展相关的产前和产后因素。创新：这将是第一次测试限制产前营养对非人类灵长类动物后代发育结果的因果影响。这项拟议的研究允许通过评估狒狒认知和行为/情感功能的新方法与人类联系起来，这些方法是评估儿童的标准方法。与NIH的使命一致，拟议的研究旨在最大限度地将结果转化为人类状况。公共卫生相关性：我们在子宫内的发育过程中经历的里程碑比我们生命中的任何其他时间都要多。在此期间营养不良会改变包括大脑在内的关键器官的发育。我们的研究是第一步，研究一个良好控制的非人灵长类动物模型的胎儿营养限制，以确定机制，在发展过程中经历的条件下，后代在以后的生活中易患异常行为，气质和认知。

DESCRIPTION (provided by applicant): The proposed study utilizes the R21 Exploratory/ Developmental Research Grant Program to explore the effects of restricted prenatal nutrition on cognitive and behavioral/emotional function of juvenile baboons. Significance: Poor nutrition during pregnancy and lactation is correlated with negative outcomes in human offspring, including cognitive deficits and behavioral and emotional problems. The implications of these findings for children's health are highly significant, but it is difficult to determine if inadequate nutrition actually causes the adverse outcomes in humans. A non-human primate model with random assignment to nutritional levels can establish causation, which in turn will lead to testable hypotheses about the mechanisms by which nutritional deficiency during pregnancy affects the fetus. In addition, data are needed on whether the risk conferred to offspring is moderated by factors during pregnancy or by the postnatal care-giving environment. Approach: We will prospectively study offspring of baboons who were randomly assigned to either moderate nutrient restriction (i.e., mothers eating 30% less than ad libitum fed mothers) or ad libitum feeding during pregnancy and lactation. Cognitive and behavioral/emotional function of juveniles will be assessed in the context of a neuropsychological battery, the Cambridge Neuropsychological Test Automated Battery, at 20 months of age (equivalent to 6 years in the human). In addition, we will test whether an association between nutrient restriction during pregnancy and developmental outcomes is moderated by maternal dominance status or postnatal care giving. The proposed study is consistent with the R21 mechanism for two reasons: first, the model, including the dependent measure of cognitive and behavioral/emotional regulation, is new and exploratory; second, the study is a necessary first step to developing a broader research program on mechanisms by which nutrition during pregnancy affects the developing brain. Environment: This project combines the skills of investigators at University of Texas at San Antonio, University of Texas Health Science Center at San Antonio and University of Chicago. The collaboration arises out of an NIMH Translation Science Network. Investigators: Dr. Bartlett has 15 years experience working with captive and wild non-human primates. Dr. Bartlett and Dr. Nijland have worked together for three years collecting data on the social behavior of socially housed baboons. Dr. Keenan's research focuses on pre- and post-natal factors associated with development of psychopathology in early childhood. Innovation: This will be the first test of the causal effects of restricted prenatal nutrition on developmental outcomes of offspring in a non-human primate. The proposed study allows links to humans through the novel use of methods for assessing cognitive and behavioral/emotional function in the baboon that are standard methods for assessing children. Consistent with the NIH mission, the proposed study is designed to maximize translation of the results to the human condition. PUBLIC HEALTH RELEVANCE: We pass more milestones during development in utero than any other time in our lives. Poor nutrition during this period alters the development of key organs including the brain. Our studies are a first step in studying a well controlled nonhuman primate model of fetal nutrient restriction to determine mechanisms by which conditions experienced during development predispose offspring to abnormal behavior, temperament, and cognition in later life.