Hepcidin treatment modulates the expression of divalent metal transporter-1, ceruloplasmin, and ferroportin-1 in the rat cerebral cortex and hippocampus

Biol Trace Elem Res. 2011 Dec;143(3):1581-93. doi: 10.1007/s12011-011-8967-3. Epub 2011 Jan 28.


Elevated iron levels are considered to play a role in the neurodegenerative mechanisms that underlie Alzheimer's and Parkinson's disease. The linkage between hepcidin (Hepc) and ferroportin-1 (FPN1), the divalent metal transporter 1 (DMT1), and ceruloplasmin (CP) in the brain is unknown. To discern the role of Hepc in regulating the expression of these proteins, we investigated FPN1, DMT1, and CP protein and mRNA expression in the brain after the intracerebroventricular injection of Hepc. Our results show that after Hepc injection, expression of FPN1 mRNA and FPN1 protein was inhibited in the cerebral cortex and hippocampus. Furthermore, we showed a clear change of DMT1 and CP protein and mRNA levels in the brain. The immunohistochemical analysis revealed an increase of DMT1 and a decrease of CP levels. Semi-quantitative analysis using PCR methods showed an increase of DMT1(+IRE) mRNA, and a decrease of DMT1(-IRE) mRNA and CP mRNA levels. Since alterations in iron levels in the brain are causally linked to degenerative conditions such as Alzheimer's disease, an improved understanding of the regulation of iron transport protein expression such as FPN1, DMT1, and CP could lead to novel strategies for treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / pharmacology*
  • Base Sequence
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Ceruloplasmin / genetics
  • Ceruloplasmin / metabolism*
  • DNA Primers
  • Hepcidins
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Immunohistochemistry
  • Male
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar


  • Antimicrobial Cationic Peptides
  • Cation Transport Proteins
  • DNA Primers
  • Hamp protein, rat
  • Hepcidins
  • RNA, Messenger
  • metal transporting protein 1
  • solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
  • Ceruloplasmin