Lead Exposure and Early Brain Development

铅暴露与早期大脑发育

• 批准号: 9252486
• 负责人: Viren Andrew D'Sa
• 金额: $ 19.21万
• 依托单位: MEMORIAL HOSPITAL OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-06 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9252486
• 关键词: Address; Affect; Age; Age-Months; Animals; Attention; Axon; Behavior assessment; Behavioral; Birth; Brain; Brain imaging; Child; Childhood; Cognitive; Cognitive deficits; Complement; Data; Dendrites; Development; Evolution; Exposure to; Health; Human; Impairment; Infant; Injury; Intervention Studies; Investigation; Knowledge; Language; Lead; Lead Poisoning; Lead levels; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Mediation; Mental Health; Methodology; Modeling; Motor; Myelin; Neuraxis; Neurites; Neurocognitive; Neurologic; Neurologic Deficit; Neurons; Neuropsychology; Outcome; Outcomes Research; Pattern; Policies; Prevention; Problem behavior; Process; Public Health; Recruitment Activity; Reporting; Research; Rhode Island; Standardization; Structural defect; Structure; Therapeutic Intervention; Time; Tissues; Toddler; Treatment Efficacy; Visuospatial; behavioral outcome; blood lead; cognitive ability; cognitive capacity; cognitive development; cognitive testing; density; early childhood; economic cost; environmental Pb exposure; executive function; fetal; follow-up; imaging study; impaired brain development; improved; infancy; insight; lead exposure; male; morphometry; myelination; neurobehavioral; neurodevelopment; neuronal growth; neurotoxic; novel; physical conditioning; postnatal; premature; programs; public health relevance; rate of change; response; screening; social; spatiotemporal; white matter

 DESCRIPTION (provided by applicant): Childhood lead exposure is associated with many adverse physical and mental health outcomes, including reduced cognitive ability and increased behavioral problems. These neurocognitive and neurobehavioral outcomes are broadly hypothesized to result from abnormalities in neurodevelopment. However, while investigations of early brain development report reduced neuronal growth and impaired white matter maturation (hypomyelination) in response to lead exposure, these studies have exclusively been performed in animals. It is unclear if, and how, these key neurodevelopmental processes are similarly altered in human children; and at what level of exposure abnormalities become significant. Thus, there are significant gaps in our knowledge regarding the neurotoxic actions of lead on the developing human brain, and how potential alterations ultimately give rise to cognitive deficits. This research aims to address these gaps by examining the relationships between blood lead level (BLL) and magnetic resonance imaging (MRI) measures of myelination and neurite (combined dendrites and axons) density in a preliminary longitudinal study following children from 12 to 24 months of age. As a first step, we will recruit 36 healthy toddlers between 10 and 14 months of age with blood lead levels between 0 and 10μg/dL, who will receive MRI and a comprehensive cognitive and behavioral assessment. BLL, MRI and neuropsychological assessments will be repeated at 12 month follow-up. From this complement of data, we will investigate the relationships linking BLL, brain structure, and cognitive ability t each age-point; as well as the relationships between the longitudinal changes in each of these measures. This study will provide the first and earliest evidence of brain structure alteration in children with varying degrees of lead exposure, and establish their relationship to concurrent measures of cognitive and behavioral functioning. We hypothesize that increased levels of blood lead will be significantly associated with reduced myelin and neurite content, and that these structural abnormalities will mediate the relationship between blood lead levels and cognitive ability. This preliminary investigation will provide crucial new insight into a pressing public health issue that carries significant social and economic cost. Results are anticipated to have far reaching consequences in regard to current screening and prevention policies.

 描述（由申请人提供）：儿童期铅暴露与许多不利的身体和心理健康结果相关，包括认知能力下降和行为问题增加，但这些神经认知和神经行为结果广泛是由神经发育异常引起的。早期大脑发育报告称，铅暴露会导致神经元生长减少和白质成熟受损（髓鞘形成不足），但这些研究仅在动物身上进行，目前尚不清楚这些关键的神经发育过程是否以及如何发生。因此，我们对铅对人类大脑发育的神经毒性作用以及潜在的改变如何最终导致认知缺陷的认识存在重大差距。在一项对 12 至 24 个月的儿童进行的初步纵向研究中，通过检查血铅水平 (BLL) 与髓鞘形成和神经突（树突和轴突组合）密度的磁共振成像 (MRI) 测量值之间的关系来解决这些差距作为第一步，我们将招募 36 名年龄在 10 至 14 个月之间、血铅水平在 0 至 10μg/dL 之间的健康幼儿，他们将接受 MRI 以及全面的认知和行为评估。我们将在 12 个月的随访中重复评估，根据这些补充数据，我们将研究每个年龄点的 BLL、大脑结构和认知能力之间的关系，以及纵向变化之间的关系。这项研究将提供不同程度铅暴露儿童大脑结构改变的第一个也是最早的证据，并建立它们与认知和行为功能的同时测量的关系。与髓磷脂和神经突含量减少显着相关，并且这些结构异常将调节血铅水平和认知能力之间的关系。这项初步研究将为解决带来重大社会和经济成本的紧迫公共卫生问题提供重要的新见解。预计将对当前筛查产生深远影响和预防政策。