MT COBRE: EFFECT OF LEAD ON DEVELOPMENT OF AUDITORY TEMPORAL PROCESSING

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Lury博士的实验室研究了极低水平的铅暴露对听觉功能的影响及其机制。利用蛋白质组学、免疫组织化学和微阵列技术，他们发现铅改变了神经细丝的磷酸化状态，改变了包括突触素和烟碱受体在内的突触蛋白的表达，并改变了运动蛋白的表达。这些马达蛋白对于将神经丝和各种突触蛋白运输到它们在细胞内的适当位置是重要的。此外，铅似乎调节连接肌动蛋白细胞骨架和各种膜蛋白的蛋白质。所有这些变化都可能对神经元通过听觉系统传递电信号的方式产生影响。他们在罗切斯特大学的合作者约瑟夫·沃尔顿博士发现，铅似乎直接影响脑干中听觉神经细胞之间的神经连接。这一点很重要，因为我们现在能够确定对可能受到铅影响的细胞系统的操纵如何改变听觉核团的神经连接。这项工作表明，极低水平的铅(低于被认为安全的水平)可以导致脑细胞内非常显著的变化。这些结果，与我们之前对鸟类中枢神经系统和鸟类行为的铅的研究相结合，导致向美国国立卫生研究院提交了一份重大拨款提案。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dr. Luries laboratory investigates the effects and mechanisms of very low levels of lead (Pb) exposure on auditory function. Using proteomic, immunohistochemistry, and microarray technology, they have found that Pb alters the phosphorylation state of neurofilament, changes the expression of synaptic proteins including synaptophysin and nicotinic receptors, and changes the expression of kinesin motor proteins. These motor proteins are important for trafficking both neurofilament and various synaptic proteins to their proper locations within the cell. In addition, Pb appears to modulate proteins that connect the actin cytoskeleton with various membrane proteins. All of these changes could have an impact on how electrical signals are transmitted by neurons through the auditory system. Their University of Rochester collaborator, Dr. Joseph Walton, has found that Pb appears to directly affect the neural connection between auditory nerve cells in the brainstem. This is important because we will now be able to determine how manipulation of cellular systems that may be affected by Pb can alter the neural connections of auditory nuclei. This work is demonstrating that very low levels of Pb (below levels that are considered safe) can result in very significant changes within brain cells. These results, combined with our previous studies of Pb on the avian CNS and on avian behavior have resulted in a submission of a major grant proposal to the NIH.