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

描述（由申请人提供）：本研究利用R21探索性/发展性研究资助计划，探讨限制性产前营养对幼年狒狒认知和行为/情绪功能的影响。意义：孕期和哺乳期营养不良与人类后代的不良结局相关，包括认知缺陷、行为和情绪问题。这些发现对儿童健康的影响是非常重要的，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类灵长类动物模型可以建立因果关系，这反过来将导致关于怀孕期间营养缺乏影响胎儿的机制的可测试假设。此外，还需要数据来说明赋予后代的风险是否受到怀孕期间因素或产后护理环境的影响。方法：我们将前瞻性研究狒狒的后代，这些狒狒在怀孕和哺乳期间被随机分配到适度营养限制（即母亲比自由喂养的母亲少吃30%）或自由喂养。青少年的认知和行为/情感功能将在20个月大（相当于人类6岁）时，在神经心理学测试的背景下进行评估，剑桥神经心理学测试自动化电池。此外，我们将测试孕期营养限制与发育结果之间的关联是否受到母体优势地位或产后护理的调节。本研究与R21机制一致的原因有二：首先，该模型包括认知和行为/情绪调节的依赖测量，是新的和探索性的；其次，这项研究是开展一个更广泛的研究项目的必要的第一步，该项目旨在研究怀孕期间的营养如何影响发育中的大脑。环境：该项目结合了圣安东尼奥德克萨斯大学、圣安东尼奥德克萨斯大学健康科学中心和芝加哥大学的研究人员的技能。这项合作源于NIMH翻译科学网络。调查人员：巴特利特博士有15年的圈养和野生非人灵长类动物研究经验。Bartlett博士和Nijland博士一起工作了三年，收集了关于群居狒狒社会行为的数据。基南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：这将是首次在非人类灵长类动物身上测试产前营养限制对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，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比生命中的任何时候都要经历更多的里程碑。这一时期营养不良会改变包括大脑在内的关键器官的发育。我们的研究是研究一个控制良好的非人类灵长类动物胎儿营养限制模型的第一步，以确定发育过程中经历的条件使后代在以后的生活中容易出现异常行为、气质和认知的机制。

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.