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KMID : 0379520070230030279
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한국독성학회지
2007 Volume.23 No. 3 p.279 ~ p.287
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The Effect of Systemic Iron Level on the Transport and Distribution of Copper to the Brain
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Choi Jae-Hyuck
Park Jung-Duck
Choi Byung-Sun
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Abstract
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Copper (Cu) is an essential trace element indispensable for brain development and function; either excess or deficiency in Cu can cause brain malfunction. While it is known that Cu and Fe homeostasis are strictly regulated in the brain, the question as to how systemic Fe status may influence brain Cu distribution was poorly understood. This study was designed to test the hypothesis that dietary Fe condition affects Cu transport into the brain, leading to an altered brain distribution of Cu. Rats were divided into 3 groups; an Fe-deficient (Fe-D) group which received an Fe-D diet (3~5 ㎎ Fe/㎏), a control group that was fed with normal diet (35 ㎎ Fe/㎏), and an Fe-overload group whose diet contained an Fe-O diet (20 g carbonyl Fe/㎏). Following a 4-week treatment, the concentration of Cu/Fe in serum, CSF (cerebrospinal fluid) and brain were determined by AAS, and the uptake rates of Cu into choroids plexus (CP), CSF, brain capillary and parenchyma were determined by an in situ brain perfusion, followed by capillary depletion. In Fe-D and Fe-O, serum Fe level decreased by 91% (p ＜ 0.01) and increased by 131% (p ＜ 0.01), respectively, in comparison to controls. Fe concentrations in all brain regions tested (frontal cortex, striatum, hippocampus, mid brain, and cerebellum) were lower than those of controls in Fe-D rats (p ＜ 0.05), but not changed in Fe-O rats. In Fe-D animals, serum and CSF Cu were not affected, while brain Cu levels in all tested regions (frontal cortex, striatum, hippocampus, mid brain, and cerebellum) were significantly increased (p ＜ 0.05). Likewise, the unidirectional transport rate constants (Kin) of Cu in CP, CSF, brain capillary and parenchyma were significantly increased (p ＜ 0.05) in the Fe-D rats. In contrast, with Fe-O, serum, CSF and brain Cu concentrations were significantly decreased as compared to controls (p ＜ 0.05). Cu transport was no significant change of Cu transport of serum in Fe-O rats. The mRNA levels of five Cu-related transporters were not affected by Fe status except DMT1 in the CP, which was increased in Fe-D and decreased in Fe-O. Our data suggest that Cu transport into brain and ensuing brain Cu levels are regulated by systemic Fe status. Fe deficiency appears to augment Cu transport by brain barriers, leading to an accumulation of Cu in brain parenchyma.
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KEYWORD
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Copper, Iron, Transport, Distribution, Brain
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