AMPA-induced excitotoxicity increases nuclear levels of CAD, Endonuclease G, and acinus and induces chromatin condensation in rat hippocampal pyramidal neurons

W. M. Henne, S. Oomman, J. Attridge, V. Finckbone, P. Coates, R. Bliss, H. Strahlendorf, J. Strahlendorf

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Programmed cell death has been linked to AMPA-receptor-mediated excitotoxicity in pyramidal neurons of the hippocampus. The intent of this study was to investigate the roles of caspase-dependent and independent nuclear death-related factors in mediating AMPA-induced nuclear changes in PyNs by use of immunohistochemistry and transmission electron microscopy (TEM). Data indicate increases in the nuclear levels of caspase-activated acinus and DNase and Endonuclease G (a caspase-independent endonuclease) in CA1 and CA3 PyN nuclei with different temporal patterns following an AMPA-insult. Hoechst staining and TEM confirm AMPA-induced chromatin condensation. The presence of active acinus in nuclei suggests it mediates chromatin condensation. Interestingly, a DNA fragmentation labeling protocol showed that there was no chromatin cleavage up to 90 min after AMPA-insult. Overall, we conclude that: 1) AMPA-induced excitotoxicity increases nuclear immunoreactivity of pro-death enzymes from multiple programmed cell death pathways, 2) differential chromatin condensation patterns occur between CA1 and CA3, and 3) there is no chromatin cleavage within our experimental timeframe.

Original languageEnglish (US)
Pages (from-to)321-339
Number of pages19
JournalCellular and Molecular Neurobiology
Volume26
Issue number3
DOIs
StatePublished - May 2006

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Keywords

  • AMPA
  • Acinus
  • CAD (caspase-activated deoxyribonuclease)
  • Endonuclease G
  • Excitotoxicity
  • Hippocampus

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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