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

描述(由申请者提供)：本研究计划利用R21探索/发展研究资助计划，探讨产前营养限制对幼龄狒狒认知和行为/情绪功能的影响。意义：怀孕和哺乳期间营养不良与人类后代的负面后果相关，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导致了人类的不良后果。随机分配营养水平的非人类灵长类动物模型可以确定因果关系，这反过来将导致关于怀孕期间营养不足影响胎儿的机制的可验证假说。此外，还需要数据说明孕期因素或产后照料环境是否降低了对子女的风险。方法：我们将前瞻性地研究被随机分配到中等营养限制(即，母亲在怀孕和哺乳期间随意喂养的母亲少吃30%)或随意喂养的狒狒后代。青少年的认知和行为/情绪功能将在20个月大(相当于人类6岁)的剑桥神经心理测试自动化电池的背景下进行评估。此外，我们将测试怀孕期间营养限制和发育结果之间的联系是否受到母亲优势地位或出生后护理的影响。拟议的研究与R21机制是一致的，原因有两个：第一，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；第二，这项研究是开发更广泛的研究计划的必要的第一步，研究怀孕期间营养影响发育中的大脑的机制。环境：这个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。这一合作源于NIMH翻译科学网络。调查人员：巴特利特博士有15年与圈养和野生非人类灵长类动物打交道的经验。Bartlett博士和Nijland博士已经合作了三年，收集关于社会安置的狒狒的社会行为的数据。基南博士的研究重点是出生前和出生后的因素，这些因素与儿童早期精神病理学的发展有关。创新：这将是第一次在非人类灵长类动物中测试限制产前营养对后代发育结果的因果影响。这项拟议的研究允许通过新的方法与人类联系起来，这些方法用于评估狒狒的认知和行为/情绪功能，这些方法是评估儿童的标准方法。与美国国立卫生研究院的任务一致，拟议的研究旨在最大限度地将结果转化为人类状况。与公共健康相关：我们在子宫发育过程中通过的里程碑比我们一生中的任何时候都多。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。我们的研究是研究良好控制的胎儿营养限制的非人类灵长类动物模型的第一步，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.