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Sullivan, Brendan T. PhD, Purdue University, May 2016. Characterization of Cu-rich aggregates in neurogenic niches of the rodent brain by X-ray fluorescence microscopy. Major Professor: Yulia Pushkar. Copper is an essential element in the brain playing several critical roles ranging from neurotransmitter synthesis to ATP production. As Cu is typically present in micromolar concentrations and has a spatially capricious distribution in the brain, determining concentrations has historically been challenging. X-ray fluorescence microscopy (XRF) offers excellent spatial resolution (down to 30 nm) and detection limits (sub parts per million), making it an excellent tool for analyzing metal distributions in the brain. Using XRF, it is demonstrated that Cu-rich aggregates with concentrations in the hundreds of millimolar are present in the subventricular zone of rats and mice. As the subventricular zone is a neurogenic niche in the adult brain, the hippocampal dentate gyrus and rostral migratory stream were also examined to see if these aggregates were present. It is shown that rats, but not mice, have Cu accumulations in the rostral migratory stream and dentate gyrus, which may be related to the fact that the rat hippocampus produces more neurons and new neurons are integrated more readily into neural circuits. In addition, these aggregates are found in glial fibrillary acidic protein-positive cells and a lack of co-localization with bromodeoxyuridine suggests they are specifically in type-B progenitor cells in the SVZ. Co-localization experiments with lysosomal associated membrane protein 1 and ubiquitin suggest that Cu aggregates are not simply awaiting autophagy but likely serve some purpose. (XANES) spectra recorded directly from Cu aggregates in tissue show that Cu is present as a CuxSy multimetallic cluster and has the oxidation state Cu . Consistent with being bound as a cuprous-thiolate cluster, Cu aggregates consistently co-localize with sulfur with a molar ratio of [S]/[Cu] = 1.66 ± 0.07. By co-localizing