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。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 表示子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 虽然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，过量的锰暴露会产生类似于特发性 帕金森氏症锰中毒是一种神经退行性疾病， 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，任何人都可能遇到锰污染的风险 水，来自燃料添加剂甲基三羰基锰和来自锰 亚乙基二硫代氨基甲酸酯是一种杀虫剂。此外，对金属的监管减弱 老年人的体内平衡使该群体更容易受到环境锰升高的影响 暴露导致出现帕金森综合征的神经症状。 锰的确切神经毒性机制尚不确定，但有迹象表明， Mn含量可影响铁、锌和铜的体内平衡。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 的Mn。因此，至关重要的是，微SXRF允许同时检测 脑组织中的Mn、Fe和Cu离子。 根据这一建议，在体内建立了慢性锰中毒大鼠脑的冠状切片， 暴露模型和健康对照将用X射线荧光技术成像。我们将 高空间分辨率测定大鼠脑内锰的分布， 氧化状态的微型XANES在大脑的不同部位，并寻找内容 与慢性锰暴露有关的其他金属（Fe，Cu，Zn）的变化。

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.