Ceruloplasmin deficiency reduces levels of iron and BDNF in the cortex and striatum of young mice and increases their vulnerability to stroke

Sarah J. Texel, Jian Zhang, Simonetta Camandola, Erica L. Unger, Dennis D. Taub, Raymond C Koehler, Z. Leah Harris, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Ceruloplasmin (Cp) is an essential ferroxidase that plays important roles in cellular iron trafficking. Previous findings suggest that the proper regulation and subcellular localization of iron are very important in brain cell function and viability. Brain iron dyshomeostasis is observed during normal aging, as well as in several neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, coincident with areas more susceptible to insults. Because of their high metabolic demand and electrical excitability, neurons are particularly vulnerable to ischemic injury and death. We therefore set out to look for abnormalities in the brain of young adult mice that lack Cp. We found that iron levels in the striatum and cerebral cortex of these young animals are significantly lower than wild-type (WT) controls. Also mRNA levels of the neurotrophin brain derived neurotrophic factor (BDNF), known for its role in maintenance of cell viability, were decreased in these brain areas. Chelator-mediated depletion of iron in cultured neural cells resulted in reduced BDNF expression by a posttranscriptional mechanism, suggesting a causal link between low brain iron levels and reduced BDNF expression. When the mice were subjected to middle cerebral artery occlusion, a model of focal ischemic stroke, we found increased brain damage in Cp-deficient mice compared to WT controls. Our data indicate that lack of Cp increases neuronal susceptibility to ischemic injury by a mechanism that may involve reduced levels of iron and BDNF.

Original languageEnglish (US)
Article numbere25077
JournalPLoS One
Volume6
Issue number9
DOIs
StatePublished - Sep 16 2011

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ferroxidase
Ceruloplasmin
neurotrophins
Brain-Derived Neurotrophic Factor
stroke
cortex
Iron
Stroke
Brain
iron
brain
mice
Cell Survival
neurons
Middle Cerebral Artery Infarction
Huntington Disease
Nerve Growth Factors
Wounds and Injuries
Chelating Agents
Familial apoceruloplasmin deficiency

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ceruloplasmin deficiency reduces levels of iron and BDNF in the cortex and striatum of young mice and increases their vulnerability to stroke. / Texel, Sarah J.; Zhang, Jian; Camandola, Simonetta; Unger, Erica L.; Taub, Dennis D.; Koehler, Raymond C; Harris, Z. Leah; Mattson, Mark P.

In: PLoS One, Vol. 6, No. 9, e25077, 16.09.2011.

Research output: Contribution to journalArticle

Texel, Sarah J. ; Zhang, Jian ; Camandola, Simonetta ; Unger, Erica L. ; Taub, Dennis D. ; Koehler, Raymond C ; Harris, Z. Leah ; Mattson, Mark P. / Ceruloplasmin deficiency reduces levels of iron and BDNF in the cortex and striatum of young mice and increases their vulnerability to stroke. In: PLoS One. 2011 ; Vol. 6, No. 9.
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