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

Illinois Institute Of Technology, Chicago IL

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Abstract

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[unreadable]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 [unreadable] 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.