UC Davis Center for Children's Environmental Health (CCEH)

加州大学戴维斯分校儿童环境健康中心 (CCEH)

• 批准号: 7476546
• 负责人: Isaac N Pessah
• 金额: $ 71.08万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7476546
• 关键词: UC; Davis; Center; Children; Environmental

DESCRIPTION (provided by applicant) The mission of the University of California-Davis Center for Children's Environmental Health (CCEH) is to promote daily interactions among a multidisciplinary team of scientists whose main research interest is to understand the complex web of etiologic factors that contribute to autism. The shared philosophy among Center participants is that a better understanding of the immunological and neurobiological mechanisms associated with this neurodevelopmental disorder can not only lead to a better understanding of the mechanisms that influence it but can also accelerate the discovery of effective intervention strategies. The goals of the CCEH in the next five years are to: (1) better understand the mechanisms by which environmental, immunologic, and molecular factors interact to influence the risk and severity of autism; (2) identify early immunologic, environmental, and genomic markers of susceptibility to autism; (3) develop mouse models of immunologic susceptibility to environmental triggers and define the impact of these triggers on the development of complex behaviors, key brain structures and neurotransmitter receptors relevant to autism; (4) translate the research findings into diagnostic tools that can be used in clinical practice to predict early autism risk; and (5) supply the community with accurate and timely information about autism risk factors. The CCEH has organized three interrelated hypothesis-based Research Projects that are supported by five Facility Cores (Administrative, Community Outreach and Translation, Analytical Chemistry, Molecular Genomics, and Statistics). The projects are: Project 1, Environmental Epidemiology of Autism, will build upon the investigators' discovery of immunologic and molecular biomarkers specific to children with autism found in 2-5 year olds enrolled in the CHARGE (Childhood Autism Risks from Genetics and Environment) study. Working closely with the Community Outreach and Translation Core and Project 2, newborn bloodspots and a second set of blood samples (CHARGE-BACK study) from CHARGE children will examine the stability over time of these biomarkers. CHARGE-BACK blood samples will also provide peripheral immune cells to study how autism alters properties of cell activation, and susceptibility to known immunotoxicants. The investigators will launch a new cohort study called Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) that tracks 200 women at high risk of giving birth to an autistic child, starting from early pregnancy and following the pregnancies and the babies to the age of three years. Project 2, Immunological Susceptibilities in Autism, will work closely with Project 1 to test the overall hypothesis that autistic children have fundamental defects in cellular immunity that ultimately lead to abnormalities in immune dysfunction and heightened susceptibility to environmental triggers. Project 3, Models of Neurodevelopmental Susceptibility, will develop and use mouse models to understand the relationships between immune system dysfunction and perinatal exposure to environmental toxicants in the development of neurobehavioral disorders in sociability and seizure susceptibility. Working closely with Project 2, the investigators will test mouse strains with low (C57BL/6J) or high (SJL mice) susceptibility to autoimmunity to determine how perinatal exposures to methylmercury, noncoplanar PCB, or polybrominated diphenyl ether 47 (BDE 47) influence brain development, complex social behaviors, and immune system function.

描述（由申请人提供） 加州大学戴维斯分校儿童环境健康中心（CCEH）的使命是促进一个多学科科学家团队之间的每日互动，他们的主要研究兴趣是了解有助于自闭症的复杂病因学因素网络。中心参与者之间的共同哲学是，对与这种神经发育障碍相关的免疫和神经生物学机制有更好的了解不仅可以更好地理解影响它的机制，而且还可以加速发现有效的干预策略。 CCEH在未来五年内的目标是：（1）更好地了解环境，免疫和分子因素相互作用以影响自闭症的风险和严重性的机制； （2）确定对自闭症易感性的早期免疫，环境和基因组标记； （3）开发了对环境触发器的免疫敏感性的小鼠模型，并定义了这些触发因素对复杂行为，关键大脑结构和神经递质受体的发展的影响； （4）将研究结果转化为诊断工具，可以在临床实践中用于预测早期自闭症风险； （5）为社区提供有关自闭症风险因素的准确和及时信息。 CCEH组织了三个相互关联的基于假设的研究项目，这些研究项目得到了五个设施核心（行政，社区外展和翻译，分析化学，分子基因组学和统计数据）的支持。 这些项目是：项目1，自闭症的环境流行病学，将基于研究人员发现对2-5岁儿童的特定自闭症儿童的免疫和分子生物标志物（遗传学和环境的儿童自闭症风险）。 与社区宣传和翻译核心和项目2紧密合作，新生儿的血点和第二组血液样本（Chunder-Back研究）将检查这些生物标志物的稳定性。抵抗血液样本还将提供外周免疫细胞，以研究自闭症如何改变细胞活化的特性以及对已知免疫毒性的敏感性。 研究人员将在婴儿学习早期体征（大理石）中发起一项新的队列研究，称为自闭症风险标记，该研究追踪200名具有自闭症儿童的高风险的女性，从怀孕早期开始，在怀孕和婴儿之后，到三岁。 项目2，自闭症中的免疫学敏感性，将与项目1紧密合作，以检验总体假设，即自闭症儿童具有细胞免疫的根本缺陷，最终导致免疫功能障碍和对环境触发因素的敏感性增强。 项目3，即神经发育敏感性的模型，将开发和使用小鼠模型，以了解免疫系统功能障碍与围产期暴露于环境有毒物质在社交性和癫痫敏感性中神经行为疾病发展中的关系。 研究人员将与项目2紧密合作，将测试低（C57BL/6J）或高（SJL小鼠）自身免疫性敏感性的小鼠菌株，以确定围产期暴露于甲基汞，非稳态PCB，或多溴溴化的二苯基二苯基47（BDE 47）47（BDE 47）（BDE 47）（BDE 47）影响脑发育，并影响社会发展，以及社交行为。