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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。Lurie博士的实验室研究了极低水平的铅（Pb）暴露对听觉功能的影响和机制。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，并改变了驱动蛋白运动蛋白的表达。这些马达蛋白对于将神经丝和各种突触蛋白运输到细胞内的适当位置是重要的。此外，铅似乎调节蛋白质连接肌动蛋白细胞骨架与各种膜蛋白。所有这些变化都可能对神经元通过听觉系统传输电信号的方式产生影响。他们的罗切斯特大学合作者约瑟夫·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。这是很重要的，因为我们现在将能够确定如何操纵可能受到铅影响的细胞系统可以改变听觉核的神经连接。这项工作表明，极低水平的铅（低于被认为是安全的水平）可以导致脑细胞内非常显着的变化。这些结果，结合我们以前的研究铅对鸟类的中枢神经系统和鸟类的行为，导致提交了一个重大的拨款建议，美国国立卫生研究院。

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. Lurie¿s 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.