RT Journal Article
SR Electronic
T1 Alterations in copper uptake, content and distribution in the brains of aging mice
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1759
OP 1759
VO 51
IS supplement 2
A1 Li-Ming Wang
A1 Qi Wu
A1 John Hoffman
A1 Paul Christian
A1 Sabine Becker
A1 Kathryn Morton
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/1759.abstract
AB 1759 Objectives Elderly individuals are more vulnerable to brain injury from oxidative stress. Copper containing enzymes in the brain protect against reactive oxygen species. This study compared copper uptake and copper-containing enzyme levels in the brains of young and aging mice. Methods Copper-67 was administered intravenously to 2, 7-9, and 14 month old mice. Copper-67 uptake in the brain was measured at 24 h by phosphor autoradiography. Cerebral superoxide dismutase-1 and cytochrome-C oxidase subunit-1 levels were measured by immunohistochemistry. Total cerebral copper distribution was analyzed by imaging laser ablation inductively coupled plasma mass spectroscopy. Results In aging mice, active 67Cu uptake and superoxide dismutase-1 levels were significantly decreased in the brain, whereas blood 67Cu and cytochrome-C oxidase subunit-1 levels were similar for all mice, irrespective of age. However, total copper content in the brain of aging mice was increased, although focal areas of decreased copper were noted in the straitum and ventral cortex. Conclusions Regulation of active Cu uptake by the brain may be linked to total copper levels in an attempt to maintain Cu homeostasis. In aging, dysregulated Cu homeostatsis may result in an increase in overall Cu uptake, although specific regions may show Cu deficits. Decreased superoxide-dismutase-1 levels in aging mice appear to parallel active uptake of Cu, which may better define a labile pool of bioavailable Cu than does total Cu content. This study illustrates the importance of a multi-modality approach to studying the biodistribution and flux of Cu in the brain. Research Support NIH grant support for this project: R21EB005728-01-A