DEVELOPMENTAL NEUROTOXICITY OF LEAD AND METHYL NERCURY

铅和甲基汞的发育神经毒性

• 批准号: 6301780
• 负责人: Bettaiya Rajanna
• 金额: $ 23.45万
• 依托单位: ALCORN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6301780
• 关键词: atomic absorption spectrometry; brain; cerebellum; developmental neurobiology; environmental toxicology; fluorescence spectrometry; frontal lobe /cortex; hippocampus; inositol phosphates; laboratory rat; lead poisoning; mercury poisoning; neurochemistry; neurotoxicology; nitric oxide; protein kinase C; receptor binding; scintillation spectrometry; second messengers; ultraviolet spectrometry

Developmental Neurotoxicity of Lead and Methyl Mercury Lead (PB) and methyl mercury (MM) are well known environmental contaminants. Exposure to these metals has been shown to affect developing brains to a greater extent. Children are more sensitive to Pb than adults whereas, both children and adults are sensitive to MM. A number of second messenger systems have been shown to play a key role in the development of the brain. However, the underlying mechanism of neurotoxicity of Pb or MM is not well understood. Our hypothesis is that developmental exposure to Pb or MM affect signal transduction process, possibly related to the modulation of nitric oxide as well as alterations in receptor-mediated phosphoinositide hydrolysis and protein kinase C. In order to test our hypothesis, we propose the following specific aims: a) Low levels of pb or MM exposure to rats during developmental results in alteration of second messenger system; and b) Conduct in vitro studies to determine the direct or indirect effects of Pb or MM on the second messenger systems. Experimental design include: a) Treat the sam perinatally with two doses of Pb (0.1% and 0.2%) or MM (0.01% and 0.02%) through drinking water from gestation day 6 up to weaning (postnatal day 20);b) Determine the neurochemical parameters such as nitric oxide synthase, inositol polyphosphate receptor binding activities, phosphoinositide (PI) hydrolysis, phospholipase C, protein kinase C and nitric oxide-mediated PI hydrolysis in hippocampus, cerebellum and frontal cortex at 2,5,10,15,20,25,30, and 60 postnatal days; c) Study the concentration- response of Pb or MM on the neurochemical parameters listed in b. In this study, nanomolar concentrations of metals will be used; d) Determine the concentrations of Pb and MM in blood and brain of rats in order to correlated in vivo and in vitro results. Two undergraduates and two graduate students will be involved in this research as student research participants. After an initial period of training, these students are expected to complete certain experiments on their own. The experiences gained in this research will motivate them to choose careers in biomedical Sciences.

铅和甲基汞的发育神经毒性 铅(PB)和甲基汞(MM)是众所周知的环境污染物 污染物。研究表明，接触这些金属会影响发育。 大脑在更大程度上。儿童比成年人对铅更敏感 然而，孩子和成年人都对MM很敏感。 信使系统已被证明在开发 大脑。然而，铅或MM神经毒性的潜在机制 还没有被很好地理解。我们的假设是，发育过程中暴露于 PB或MM影响信号转导过程，可能与 一氧化氮的调节及其受体介导的变化 磷脂酰肌醇水解酶和蛋白激酶C。 假设，我们提出以下具体目标：a)低水平的铅或 大鼠发育过程中暴露于MM可引起第二秒的改变 信使系统；以及b)进行体外研究以确定直接的 或铅或MM对第二信使系统的间接影响。 实验设计包括：a)围产期两次给药 铅(0.1%和0.2%)或MM(0.01%和0.02%) 妊娠第6天至断奶(出生后第20天)；b)确定 一氧化氮合酶、肌醇等神经化学参数 多聚磷受体结合活性，磷脂酰肌醇(PI) 水解酶、磷脂酶C、蛋白激酶C和一氧化氮介导的猪 海马区、小脑和额叶皮质的水解酶 出生后2、5、10、15、20、25、30和60天；c)研究浓度- 铅或MM对b.中所列神经化学参数的反应 研究，将使用金属的纳摩尔浓度；d)确定 铅和MM在大鼠血和脑中的浓度 相关的体内和体外结果。两个本科生和两个 研究生将作为学生研究参与这项研究。 参与者。经过最初一段时间的培训，这些学生 期望自己完成某些实验。体验 这项研究将激励他们选择生物医学领域的职业 科学。