Nonhuman Primate Core

总结：非人灵长类动物核心 有一个关键的未满足的需求，即开发日益复杂的动物模型， 可能是精神分裂症（SZ）发展的基础，并为精神分裂症的发展提供信息的大脑机制。 针对这种疾病的新的治疗干预。虽然这种疾病的根本原因尚不清楚， 汇集的证据表明，SZ是一种神经发育性脑疾病， 遗传和环境风险因素。我们的团队正在使用跨物种的互补方法， 检查SZ的一个潜在病因-产前免疫环境的变化，改变大脑和 后代的行为发展。流行病学研究的证据表明， 怀孕期间的各种感染与孩子以后发展SZ的风险增加有关。 啮齿类动物模型在建立激活的母体细胞之间的因果关系方面发挥了关键作用。 免疫系统和后代异常的大脑和行为发育。的长远目标 非人灵长类动物（NHP）核心是弥合人类研究和啮齿类动物模型之间的差距，并评估 在与人类更密切相关的模型系统中，母体免疫激活（MIA）的疾病相关性 - 恒河猴为了实现这一目标，我们将实现三个具体目标。首先是NHP核心 将从出生前暴露于以下物质的恒河猴的初始队列中取样并分发存档的脑组织： MIA与项目1和2的比较，以评价MIA异常行为的细胞和分子病理学基础 后代其次，NHP核心将产生一个新的MIA和对照猕猴后代群体， 在项目3中进行一系列高度整合的结构、功能和分子神经影像学研究 和4.最后，NHP核心将对儿童的行为发展进行全面评估， MIA和对照猕猴后代的新队列使用探索SZ核心特征的新措施。 这种对产前暴露于MIA的猴子的大脑和行为发育的相互关联的评估将 为SZ动物模型提供了进一步的支持，该模型具有高的结构、面部和预测可靠性。通过 为了实现这些目标，国家水文计划的核心将为了解MIA的影响和 其可能有助于SZ的病理生理学的机制。如果成功，这将导致 开发用于开发SZ诊断生物标志物和创新治疗的新靶点 和其他神经发育障碍。

SUMMARY: NONHUMAN PRIMATE CORE There is a critical unmet need to develop increasingly sophisticated animal models that will provide insights in the brain mechanisms that may underlie the development of schizophrenia (SZ) and inform the development of novel therapeutic interventions for this illness. While the underlying causes of the illness remain unknown, converging evidence suggests that SZ is a neurodevelopmental brain disease resulting from a combination of genetic and environmental risk factors. Our group is using cross-species, complimentary approaches to examine one potential etiology of SZ – changes in the prenatal immune environment that alter brain and behavioral development of the offspring. Evidence from epidemiological studies has shown that exposure to a variety of infections during pregnancy is associated with an increased risk of having a child later develop SZ. Rodent models have played a critical role in establishing causal relationships between the activated maternal immune system and aberrant brain and behavior development in the offspring. The long term objective of the Nonhuman Primate (NHP) Core is to bridge the gap between human studies and rodent models, and evaluate the disease relevance of maternal immune activation (MIA) in a model system more closely related to humans – the rhesus monkey. To accomplish this objective, we will undertake three specific aims. First the NHP core will sample and distribute archived brain tissue from an initial cohort of rhesus monkeys prenatally exposed to MIA to Projects 1 and 2 to evaluate the cellular and molecular pathology underlying aberrant behaviors of MIA offspring. Second, the NHP core will generate a new cohort of MIA and control macaque offspring needed to carry out a highly integrated series of structural, functional and molecular neuroimaging studies in Projects 3 and 4. Finally, the NHP core will conduct a comprehensive assessment of the behavioral development of the new cohort of MIA and control macaque offspring using novel measures that probe the core features of SZ. This interconnected evaluation of brain and behavioral development of monkeys prenatally exposed to MIA will provide further support for an animal model of SZ with high construct, face and predictive reliability. By accomplishing these aims the NHP core will contribute important new insights into the effects of MIA and the mechanisms by which it may contribute to the pathophysiology of SZ. If successful this will lead to the development of novel targets for the development of diagnostic biomarkers and innovative treatments for SZ and other neurodevelopmental disorders.