Coexistence of Copper in the Iron-Rich Particles of Aceruloplasminemia Brain.
The interaction between iron and copper has been discussed in association with human health and diseases for many years. Ceruloplasmin, a multi-copper oxidase, is mainly involved in iron metabolism and its genetic defect, aceruloplasminemia (ACP), shows neurological disorders and diabetes associated with excessive iron accumulation, but little is known about the state of copper in the brain. Here, we investigated localization of these metals in the brains of three patients with ACP using electron microscopes equipped with an energy-dispersive x-ray analyzer. Histochemically, iron deposition was observed mainly in the basal ganglia and dentate nucleus, and to lesser degree in the cerebral cortex of the patients, whereas copper grains were not detected. X-ray microanalysis identified two types of iron-rich particles in their brains: dense bodies, namely hemosiderins, and their aggregated inclusions. A small number of hemosiderins and most inclusions contained a significant amount of copper which was enough for distinct Cu x-ray images. These copper-containing particles were observed more frequently in the putamen and dentate nucleus than the cerebral cortex. Coexistence of iron and copper was supported by good correlations in the molecular ratios between these two metals in iron-rich particles with Cu x-ray image. Iron-dependent copper accumulation in iron-rich particles may suggest that copper recycling is enhanced to meet the increased requirement of cuproproteins in iron overload brain. In conclusion, the iron-rich particles with Cu x-ray image were found in the ACP brain.
Department of Brain Disease Research, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. kyoshida@shinshu-u.ac.jp.|Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan. kyoshida@shinshu-u.ac.jp.
Kunihiro
K
Yoshida
Department of Medicine, Aichi Gakuin University School of Pharmacy, Nagoya, Japan.
Hisao
H
Hayashi
Department of Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Shinya
S
Wakusawa
Department of Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Ryota
R
Shigemasa
Department of Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Ryoji
R
Koide
Department of Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Tetsuya
T
Ishikawa
Department of Medicine, Aichi Gakuin University School of Pharmacy, Nagoya, Japan.
Yasuaki
Y
Tatsumi
Department of Medicine, Aichi Gakuin University School of Pharmacy, Nagoya, Japan.
Koichi
K
Kato
Department of Neurology, Matsumoto Medical Center, Matsumoto, Japan.
Shinji
S
Ohara
Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan.
Shu-Ichi
SI
Ikeda
D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D002570:Ceruloplasmin / Q000172:deficiency* / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D019190:Iron Overload / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging / Q000378:metabolism*
D003300:Copper; D007501:Iron; D002570:Ceruloplasmin
Ceruloplasmin; Copper; Hemosiderin; Iron; X-ray microanalysis