MICRO-SXRF IMAGING OF RAT BRAINS AND MECHANISMS OF MANGANESE NEUROTOXICITY

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 尽管锰在人的一生中对正常发育和身体功能起着至关重要的作用 在所有哺乳动物中，过量接触锰会产生类似于特发性的症状。 S帕金森病。锰中毒是一种神经退行性疾病，目前还没有有效的治疗方法。 慢性锰暴露引起的疾病。已知风险增加的职业包括焊工 和冶炼工人。然而，任何人都可能遇到被锰污染的饮酒风险。 水，来自燃料添加剂甲基环戊二烯基锰、三羰基锰和锰 二硫代氨基甲酸乙二酯是一种杀虫剂。此外，削弱了对金属的监管 老年人的体内平衡使这一群体更容易受到环境中锰的升高的影响 暴露会导致帕金森氏症的神经症状出现。 锰的确切神经毒性机制尚不清楚，但有迹象表明， 锰含量会影响铁、锌、铜的动态平衡。基于多个 研究表明，铁代谢紊乱可能是神经毒性作用的基础。 锰的含量。因此，微SXRF允许同时检测 脑组织中的锰、铁、铜离子。 根据这一建议，建立了在体慢性锰中毒大鼠脑的冠状切片。 用X射线荧光技术对暴露模型和健康对照进行成像。我们会 用高空间分辨率测定大鼠脑内锰的分布，监测锰 微量XANES在大脑不同部位的氧化状态和寻找含量 其他金属(铁、铜、锌)的变化与慢性锰暴露有关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Although Mn plays a vital role for normal development and body functions during the life span of all mammals, excessive manganese exposure produces symptoms resembling those of idiopathic Parkinson¿s disease. There is no effective treatment for manganism, a neurodegenerative disease caused by chronic Mn exposure. Occupations with known increased risk include welders and smelting workers. However, any person can encounter risks from Mn contaminated drinking water, from the fuel additive methylcyclopentadienyl manganese tricarbonyl and from manganese ethylene-bis-dithiocarbamate ¿ a pesticide. Additionally, weakened regulation of the metal homeostasis in elderly people makes this group more susceptible to elevated environmental Mn exposure resulting in emergence of neurological symptoms of Parkinsonism. The exact neurotoxic mechanism of Mn is uncertain but there are indications that alteration of the Mn content can affect the homeostasis of iron, zinc and copper. Based on a number of studies, it was suggested that a disturbed Fe metabolism could underlie the neurotoxic action of Mn. So, it is of critical importance that micro-SXRF allows simultaneous detection of the Mn, Fe and Cu ions in brain tissues. Under this proposal the coronal sections of rat brains of well established in vivo chronic Mn exposure model and healthy controls will be imaged with X-ray fluorescent technique. We will determine the Mn distribution in rat brain with high spatial resolution, monitor the Mn oxidation state by micro-XANES in different parts of the brain and look for content alterations of the other metals (Fe, Cu, Zn) in connection with chronic Mn exposure.