title: Copper accumulation in rodent brain astrocytes: A species difference.
abstract: Changes in Cu homeostasis have been implicated in multiple neurodegenerative diseases. Factors controlling and regulating the distribution of Cu in the brain remain largely unknown. We have previously reported that a sub-set of astrocytes in the subventricular zone (SVZ) contain Cu-rich aggregates. Here we expand previous studies with detailed X-ray fluorescent imaging (XRF) analysis of the additional brain areas of hippocampus (HP) and rostral migratory stream (RMS). We also use conventional DAB (3,3'-diaminobenzidine) staining which accesses both peroxidase and pseudo-peroxidase activities. Both the HP and RMS support neurogenesis while the latter also serves as a migratory pathway for neuronal precursors. Some variations in neurogenic activities have been noticed between species (such as mice and rats). We report here that in rats, the HP, rostral migratory stream (RMS) and third ventricle contain glia which stain positively for DAB and contain copper-rich aggregates as measured by XRF. In contrast, mice hippocampi and RMS display neither DAB+ aggregates nor Cu-rich accumulations via XRF. DAB+ aggregates were not induced in the HP of mice transgenic for human amyloid precursor protein (APP) and presenilin, suggesting that accumulations positively stained for DAB are not directly caused by APP. These observed critical differences suggest different properties of the astrocytes in two species. Results suggest that the rat model may have important advantages over the mouse model for the study of hippocampal aging and neurodegeneration.
authors.affiliation: Department of Physics and Astronomy, Purdue University, 525 Northwestern Ave., West Lafayette, IN 47907, United States.
authors.forename: Brendan
authors.initials: B
authors.lastname: Sullivan
authors.affiliation: Department of Physics and Astronomy, Purdue University, 525 Northwestern Ave., West Lafayette, IN 47907, United States; Department of Physics, Hanover College, Hanover, IN, United States.
authors.forename: Gregory
authors.initials: G
authors.lastname: Robison
authors.affiliation: Department of Physics and Astronomy, Purdue University, 525 Northwestern Ave., West Lafayette, IN 47907, United States. Electronic address: ypushkar@purdue.edu.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Pushkar
authors.affiliation: Department of Anatomy, Howard University College of Medicine 520 W St., NW, Washington DC 20059, United States.
authors.forename: John K
authors.initials: JK
authors.lastname: Young
authors.affiliation: Department of Physiology, Howard University College of Medicine 520 W St., NW, Washington DC 20059, United States.
authors.forename: Kebreten F
authors.initials: KF
authors.lastname: Manaye
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology*; D003300:Copper / Q000378:metabolism*; D005453:Fluorescence; D008297:Male; D057054:Molecular Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014965:X-Rays
chemical_list: D003300:Copper
keywords: Alzheimer’s; Gomori-positive glia; Hippocampal aging; Neurogenesis; X-ray fluorescence