Ceruloplasmin deficiency results in an anxiety phenotype involving deficits in hippocampal iron, serotonin, and BDNF

Sarah J. Texel, Simonetta Camandola, Bruce Ladenheim, Sarah M. Rothman, Mohamed R. Mughal, Erica L. Unger, Jean Lud Cadet, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Ceruloplasmin (Cp) is a ferroxidase involved in iron metabolism by converting Fe 2+ to Fe 3+, and by regulating cellular iron efflux. In the ceruloplasmin knockout (CpKO) mouse, the deregulation of iron metabolism results in moderate liver and spleen hemosiderosis, but the impact of Cp deficiency on brain neurochemistry and behavior in this animal model is unknown. We found that in contrast to peripheral tissues, iron levels in the hippocampus are significantly reduced in CpKO mice. Although it does not cause any discernable deficits in motor function or learning and memory, Cp deficiency results in heightened anxiety-like behavior in the open field and elevated plus maze tests. This anxiety phenotype is associated with elevated levels of plasma corticosterone. Previous studies provided evidence that anxiety disorders and long-standing stress are associated with reductions in levels of serotonin (5HT) and brain-derived neurotrophic factor (BDNF) in the hippocampus. We found that levels of 5HT and norepinephrine (NE), and the expression of BDNF and its receptor trkB, are significantly reduced in the hippocampus of CpKO mice. Thus, Cp deficiency causes an anxiety phenotype by a mechanism that involves decreased levels of iron, 5HT, NE, and BDNF in the hippocampus.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalJournal of Neurochemistry
Issue number1
StatePublished - Jan 2012


  • anxiety
  • BDNF
  • iron
  • learning and memory
  • norepinephrine
  • serotonin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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