Neurotoxicity Research

, Volume 19, Issue 4, pp 527–535 | Cite as

Neonatal Iron Treatment Increases Apoptotic Markers in Hippocampal and Cortical Areas of Adult Rats

  • Clivia Pazin Miwa
  • Maria Noêmia Martins de Lima
  • Felipe Scalco
  • Gustavo Vedana
  • Raquel Mattos
  • Liana Lisboa Fernandez
  • Arlete Hilbig
  • Nadja Schröder
  • Monica R. M. Vianna


Oxidative stress, cellular damage, and neuronal apoptosis are believed to underlie the progressive cognitive decline that accompanies natural aging and to be exacerbated in neurodegenerative diseases. Over the years, we have consistently demonstrated that iron neonatal treatment induces oxidative stress and memory deficits in adult rats, but the mechanisms underlying these effects remained undefined. The purpose of this study was to examine whether neonatal iron overload was associated with apoptotic cell death in adult and old rats. We analyzed Par-4 and caspase-3 immunoreactivity in specific brain areas including the hippocampus CA1, CA3 and dentate gyrus (DG), the adjacent cortex and the striatum in adult (3 months-old) and aged (24 months-old) rats from control (vehicle-treated) and neonatally iron-treated groups. Neonatal iron treatment consisted of a daily oral administration of 10 mg/kg of Fe+2, for three consecutive days, from post-natal 12–14. Control aged animals showed increased levels of both markers when compared to untreated adult animals. When adults were compared, iron-treated animals presented significantly higher Par-4 and caspase-3 immunoreactivities in CA1, CA3 and cortex. In the DG, this effect was statistically significant only for Par-4. Interestingly, when control and iron-treated aged animals were compared, a significant decrease in both apoptotic markers was observed in the later groups in the same areas. These results may be interpreted as an acceleration of aging progressive damages caused by iron overload and may contribute to a better understanding of the damaging potential of iron accumulation to brain function and the resulting increased susceptibility to neurodegeneration.


Iron Neurodegeneration Aging Apoptosis Rat 



This research was partially funded by CNPq grant 476316/2006-5 and FAPERGS PROADE3 0521807 to Monica Vianna. Monica Vianna is supported by CNPq 312137/2006-0 fellowship, Nadja Schröder is supported by 301368/2006-6 fellowship, and Clivia Miwa is supported by CAPES-MEC fellowship.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Clivia Pazin Miwa
    • 1
  • Maria Noêmia Martins de Lima
    • 1
    • 3
  • Felipe Scalco
    • 1
  • Gustavo Vedana
    • 1
  • Raquel Mattos
    • 1
  • Liana Lisboa Fernandez
    • 1
    • 2
  • Arlete Hilbig
    • 2
  • Nadja Schröder
    • 1
    • 3
  • Monica R. M. Vianna
    • 1
    • 3
  1. 1.Neurobiology and Developmental Biology Laboratory, Faculty of BiosciencesPontifical Catholic UniversityPorto AlegreBrazil
  2. 2.Health Basic Science DepartmentFederal University of Medical SciencePorto AlegreBrazil
  3. 3.National Institute for Translational Medicine (INCT-TM)Porto AlegreBrazil

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