Immunohistochemical determination of the Wilson Copper-transporting P-typeATPase in the brain tissues of the rat

Immunohistochemical localization of Copper-transporting P-type ATPase (ATP7 B), a gene product responsible for Wilson disease, was visualized in the br ain tissues of the Long-Evans agouti rat in detail using tissue-blotting te chnique and confocal laser microscopy. The ATP7B was intensely detected in neuronal cells of the hippocampal formation, olfactory bulbs, cerebellum, c erebral cortex and nuclei in the brainstem in which high amounts of copper and cuproenzymes, dopamine beta hydroxylase and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) were detected. The present results suggest that ATP7B plays key roles in neurotransmissions of catecholamine pathway and preventing brain tissues from injury by superoxide radicals to regulate the cellular Cu conc entration and/or activities of cuproenzymes related to neurotransmissions a nd a free radical metabolism. Furthermore, it is reasonable to assume that neurotoxicity due to abnormal copper accumulation or irregular regulation o f cuproenzymes in the critical brain regions by mutation of the ATP7B gene leads to neurological failures of Wilson disease. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.