Comparison of the effects of elevated intracellular aluminum and calcium levels on neuronal survival and tau immunoreactivity

Mark P. Mattson, Mark A. Lovell, William D. Ehmann, William R. Markesbery

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43 Scopus citations

Abstract

Both calcium and aluminum have been implicated in the cell damage and death that occurs in several neurodegenerative disorders including Alzheimer's disease (AD). We examined the effects of experimentally elevated intraneuronal levels of aluminum ([Al]i) and/or calcium ([Ca2+]i) on neuronal degeneration and antigenic alterations in the microtubule-associated protein tau in cell cultures of rat hippocampus and human cerebral cortex. Exposure of cultures to Al3+ alone (200 μM) for up to 6 d did not result in neuronal degeneration. Neurons exposed to the divalent cation ionophore A23187 degenerated within 4 h when Ca2+ was present in the culture medium whether or not Al3+ was present. Measurements of [Ca2+i] using the calcium indicator dye fura-2 demonstrated a direct relationship between increased [Ca2+]i and neuronal degeneration. In contrast, neurons did not degenerate when exposed to A231887 in the presence of Al3+ and the absence of Ca2+, despite a 10-fold elevation in [Al]i as measured by laser microprobe mass spectrometry. Calcium influx, but not aluminum influx, elicited antigenic changes in tau similar to those seen in AD neurofibrillary tangles. Neurons exposed to glutamate in the presence of Al3+ but in the absence of Ca2+ were not vulnerable to injury. Finally, increased [Al]i] occured in neurons that degenerated as the result of exposure to glutamate indicating that aluminum associates with degenerating neurons. Taken together these data indicate that, in contrast to increased [Ca2+]i, elevated [Al]i may not induce degeneration or antigenic changes in tau.

Original languageEnglish
Pages (from-to)21-31
Number of pages11
JournalBrain Research
Volume602
Issue number1
DOIs
StatePublished - Jan 29 1993

Bibliographical note

Funding Information:
Acknowledgements. We thank P. Davies and K.S. Kosik for the generous gifts of Alz-50 and 5E2, respectively. We are particularly thankful for the excellent technical help of C. Richey, S. Bose, B. Cheng and J. Mattson. This work was supported by 1P50 AG05144, 1P01 AG05119, IR01 NS29001, and a Faculty Scholar Award to M.P.M. from the Alzheimer's Association.

Keywords

  • Alzheimer's disease
  • Excitatory amino Acid
  • Fura-2
  • Hippocampus
  • Human neuron
  • Laser microprobe mass spectrometry
  • Neuron death
  • Tau
  • Ubiquitin

ASJC Scopus subject areas

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

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