Intraneuronal aluminum potentiates iron-induced oxidative stress in cultured rat hippocampal neurons

Charles X. Xie, Mark P. Mattson, Mark A. Lovell, Robert A. Yokel

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Aluminum can facilitate Fe-mediated oxidative injury, which may contribute to Al neurotoxicity. It has been reported that Al potentiates Fe-induced oxidative stress in cultured granule cells, suggesting a mechanism for Al facilitation of Fe-mediated oxidative injury. However, the relationship of intracellular Al concentration to Fe-induced oxidative stress has not been reported. In the present study, neuronal oxidative stress and survival were investigated. Embryo rat hippocampal neuron cultures were treated with Al2(SO4)3 and/or FESO4. An ionophore, A23187, was utilized to facilitate cellular Al uptake. Intraneuronal Al concentration was ascertained by laser microprobe mass spectrometry (LMMS). Neuronal oxidative stress was measured by confocal laser scanning microscopy, using 2,7-dichlorofluorescin diacetate (DCFH-DA) as a probe. The study showed that neuronal Al uptake was facilitated by the ionophore and that an increase of intraneuronal Al concentration potentiated Fe-induced oxidative stress and neuronal death. The results indicate that Al potentiation of Fe-induced oxidative stress might contribute to Al facilitation of oxidative injury, and thus to Al neurotoxicity.

Original languageEnglish
Pages (from-to)271-277
Number of pages7
JournalBrain Research
Issue number1-2
StatePublished - 1996

Bibliographical note

Funding Information:
The authors thank Drs. Steve W. Barger and Yadong S. Goodman, Sanders Brown Center on Aging, University of Kentucky, for their technical assistance in the DCFH-DA and cell survival studies; Mary G. Engle, Department of Anatomy and Neurobiology, University of Kentucky, for LMMS section preparation; and Dr. Mary K. Rayens, Biostatistics Consulting Unit, University of Kentucky, for statistics consultation. The study was supported by NIH R01 ES4640, NIH T32 ES7266, and the University of Kentucky Medical Center Research Fund.


  • 2,7-dichlorofluorescin diacetate
  • aluminum
  • confocal laser scanning microscopy
  • hippocampal neuron
  • iron
  • laser microprobe mass spectrometry
  • oxidative stress
  • reactive oxygen species

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


Dive into the research topics of 'Intraneuronal aluminum potentiates iron-induced oxidative stress in cultured rat hippocampal neurons'. Together they form a unique fingerprint.

Cite this