Extracellular vesicle microRNA in neurodevelopmental models of cognitive deficit

项目摘要 认知是一种关键而复杂的高级大脑功能，控制着行为结果。中的几个地区 大脑，包括前额叶皮质和海马体，参与指导关键的认知过程。 这些大脑区域的功能改变会导致认知障碍，这是精神病患者的核心特征 自闭症、精神分裂症和抑郁症等疾病。来自动物和人类研究的数据表明 出生前的环境对后代的神经认知发育起着重要的作用。早期生活 压力或童年低社会经济地位与成年后认知功能受损有关。 研究还表明，产前或产后营养改变(包括营养不足/营养过剩和营养不良) 不平衡)会导致青春期和成年期的认知缺陷。因此，可能看起来截然不同的东西 妊娠期间的不安，即母亲压力或母亲营养改变，也会导致同样的结果 青少年和成年后代的行为结果，即认知缺陷。发展机制 对认知功能受损的责任尚不清楚。在人类和动物模型上的研究已经 提示神经内分泌和免疫系统参与改变后代大脑发育 在孕期处于产前应激或母体营养及代谢状态改变的情况下。这个 发现细胞外RNA(ExRNA)分子循环，进入遥远的细胞并改变其表型 改变了我们对细胞间通讯的观念，开辟了研究的新途径 发病机制和生物标志物研究。该提案将利用两个动物模型来确定 ExRNAs可能是早期生活环境影响大脑发育和认知的途径 性能。此外，由于外源RNA存在于循环血液中，我们有可能识别出 评估大脑发育轨迹的外周生物标志物。这种非侵入性生物标志物将 在临床和实验室中都有很大的价值。

Project Summary Cognition is a critical and complex higher brain function that controls behavioral outcomes. Several regions in the brain, including the prefrontal cortex and hippocampus, are involved in guiding key cognitive processes. Altered functioning in these brain areas lead to cognitive deficits which are core features in psychiatric disorders such as autism, schizophrenia and depression. Data from animal and human studies indicate that the prenatal environment plays a significant role in shaping neurocognitive development in offspring. Early life stress or low childhood socioeconomic status is associated with impaired cognitive functioning in adulthood. Studies also show that altered prenatal or postnatal nutrition (including under- /over-nutrition and nutritional imbalance) leads to cognitive deficits in adolescence and adulthood. Thus, what may appear to be distinct perturbations during gestation, i.e. maternal stress or altered maternal nutrition, can result in the same behavioral outcome in adolescent and adult offspring, i.e. cognitive deficits. The developmental mechanisms responsible for impaired cognitive function are not clear. Studies in humans and animal models have suggested the involvement of the neuroendocrine and immune systems in altering offspring brain development under conditions of prenatal stress or altered maternal nutrition and metabolic state during gestation. The finding that extracellular RNA (exRNA) molecules circulate, enter distant cells and alter their phenotype has transformed our notions of intercellular communication and opened new avenues of investigation for pathogenesis and biomarker studies. This proposal will utilize two animal models to determine whether exRNAs may be a route through which the early life environment affects brain development and cognitive performance. In addition, because exRNAs are present in circulating blood, we have the potential to identify peripheral biomarkers for assessing the trajectory of brain development. Such non-invasive biomarkers would have great value in both the clinic and the laboratory.