Extracellular vesicle microRNA in neurodevelopmental models of cognitive deficit

认知缺陷神经发育模型中的细胞外囊泡 microRNA

• 批准号: 9181222
• 负责人: Sarven Sabunciyan
• 金额: $ 24.3万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9181222
• 关键词: Adolescence; Adult; Adult Children; Affect; Aging; Animal Model; Area; Autistic Disorder; Behavior; Biological Markers; Blood; Brain; Brain region; Cells; Childhood; Clinic; Clinical; Cognition; Cognitive deficits; Communication; Complex; Development; Diagnostic; Diet and Nutrition; Disease; Distant; Environment; Etiology; Exposure to; Fetus; Future; High Fat Diet; Hippocampus (Brain); Human; Immune system; Impaired cognition; Investigation; Laboratories; Lead; Life; Life Stress; Mediating; Mental Depression; Mental disorders; Metabolic; MicroRNAs; Modeling; Mothers; Neurocognitive; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neurosecretory Systems; Nutritional; Pathogenesis; Peripheral; Phenotype; Play; Prefrontal Cortex; Pregnancy; RNA; Rattus; Role; Route; Schizophrenia; Shapes; Socioeconomic Status; Tissue Sample; adolescent offspring; animal data; behavior influence; behavioral outcome; cognitive development; cognitive function; cognitive performance; cognitive process; extracellular; extracellular vesicles; in utero; innovation; intercellular communication; maternal stress; mother nutrition; neurodevelopment; nutrition; offspring; postnatal; prenatal; prenatal stress

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.

项目摘要 认知是控制行为结果的关键和复杂的高级大脑功能。几个地区 包括前额皮质和海马体在内的大脑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缺陷，这是精神病的核心特征。 自闭症、精神分裂症和抑郁症等疾病。动物和人类研究的数据表明， 产前环境在塑造后代的神经认知发育方面起着重要作用。早期生活 压力或儿童社会经济地位低下与成年后认知功能受损有关。 研究还表明，产前或产后营养的改变（包括营养不足/营养过剩和营养不良）， 不平衡）导致青少年和成年期的认知缺陷。因此，看起来不同的是 妊娠期间的扰动，即母体压力或母体营养改变，可导致相同的 青少年和成年后代的行为结果，即认知缺陷。发展机制 导致认知功能受损的原因尚不清楚。对人类和动物模型的研究 表明神经内分泌和免疫系统参与改变后代的大脑发育 在产前压力或怀孕期间母体营养和代谢状态改变的情况下。的 发现细胞外RNA（exRNA）分子循环，进入远端细胞并改变其表型， 改变了我们对细胞间通讯的概念，并为研究 发病机制和生物标志物研究。该提案将利用两种动物模型来确定是否 exRNA可能是早期生活环境影响大脑发育和认知能力的途径。 性能此外，由于exRNA存在于循环血液中，我们有潜力识别 用于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 在临床和实验室都有很大的价值。