Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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The Effect of Systemic Iron Level on the Transport and Distribution of Copper to the Brain

체내 철 수준이 뇌로의 구리 이동과 분포에 미치는 영향

  • Choi, Jae-Hyuck (Department of Preventive Medicine, College of Medicine, Chung-Ang University) ;
  • Park, Jung-Duck (Department of Preventive Medicine, College of Medicine, Chung-Ang University) ;
  • Choi, Byung-Sun (Department of Preventive Medicine, College of Medicine, Chung-Ang University)
  • 최재혁 (중앙대학교 의과대학 예방의학교실) ;
  • 박정덕 (중앙대학교 의과대학 예방의학교실) ;
  • 최병선 (중앙대학교 의과대학 예방의학교실)
  • Published : 2007.09.30
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Abstract

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 ($3{\sim}5 mg$ Fe/kg), a control group that was fed with normal diet (35mg Fe/kg), and an Fe-overload group whose diet contained an Fe-O diet (20g carbonyl Fe/kg). 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 $(K_{in})$ 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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References

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