AMPA-induced dark cell degeneration is associated with activation of caspases in pyramidal neurons of the rat hippocampus

Jennifer Coles, Sowmini K. Oomman, William M. Henne, Richard M. Bliss, Trenton C. Hoffman, VelvetLee Finckbone, Howard Strahlendorf, Jean Strahlendorf

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Various neurons in the central nervous system (CNS) exhibit selective vulnerability to AMPA-induced delayed neurotoxicity known as dark cell degeneration. Hippocampal pyramidal neurons in the CA1 and CA3 regions display such vulnerability that encompasses morphological changes including cytoplasmic and nuclear condensation, neuronal shrinkage, formation of cytoplasmic vacuoles, and general failure of physiology. The present study was undertaken to ascertain the potential involvement of initiator (caspase-9) and executor (caspase-3) caspases in AMPA-receptor-induced dark cell degeneration in pyramidal neurons. Immunohistochemical analyses revealed that immunoreactivity of the active form of caspase-9 and -3 was increased in pyramidal neurons in CA1 and CA3 regions of the hippocampus following AMPA (100 μM). Elevated levels of active caspase-9 immunoreactivity generally preceded elevations in active caspase-3 immunoreactivity. The pan caspase inhibitor FK011 effectively attenuated AMPA-induced dark cell degeneration in both CA1 and CA3 regions. Collectively, the data suggest a role for these caspases in mediating AMPA-induced toxicity in pyramidal neurons of the rat hippocampus.

Original languageEnglish (US)
Pages (from-to)294-299
Number of pages6
JournalNeuroscience letters
Volume436
Issue number3
DOIs
StatePublished - May 16 2008

Keywords

  • AMPA
  • Caspases
  • Excitotoxicity
  • Hippocampus

ASJC Scopus subject areas

  • General Neuroscience

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