Attenuation of neurotoxicity in cortical cultures and hippocampal slices from E2F1 knockout mice

Tania F. Gendron, Geoff A.R. Mealing, James Paris, Allison Lou, Andrei Edwards, Sheng T. Hou, John P. MacManus, Antoine M. Hakim, Paul Morley

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

The E2F1 transcription factor modulates neuronal apoptosis induced by staurosporine, DNA damage and β-amyloid. We demonstrate E2F1 involvement in neuronal death induced by the more physiological oxygen-glucose deprivation (OGD) in mouse cortical cultures and by anoxia in mouse hippocampal slices. E2F1(+/+) and (-/-) cultures were comparable, in that they contained similar neuronal densities, responded with similar increases in intracellular calcium concentration ([Ca2+]i to glutamate receptor agonists, and showed similar NMDA receptor subunit mRNA expression levels for NR1, NR2A and NR2B. Despite these similarities, E2F1(-/-) cultures were significantly less susceptible to neuronal death than E2F1(+/+) cultures 24 and 48 h following 120-180 min of OGD. Furthermore, the absence of E2F1 significantly improved the ability of CA1 neurons in hippocampal slices to recover synaptic transmission following a transient anoxic insult in vitro. These results, along with our finding that E2F1 mRNA levels are significantly increased following OGD, support a role for E2F1 in the modulation of OGD- and anoxia-induced neuronal death. These findings are consistent with studies showing that overexpression of E2F1 in postmitotic neurons causes neuronal degeneration and the absence of E2F1 decreases infarct volume following cerebral ischemia.

Original languageEnglish (US)
Pages (from-to)316-324
Number of pages9
JournalJournal of neurochemistry
Volume78
Issue number2
DOIs
StatePublished - 2001

Keywords

  • Cell death
  • Cortical neurons
  • E2F1
  • Hippocampal slice
  • Oxygen-glucose deprivation
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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