Neurotoxicity Research

, Volume 5, Issue 4, pp 255–264 | Cite as

Studies on neuronal apoptoisis in primary forebrain cultures: Neuroprotective/anti-apoptotic action of NR2B NMDA antagonists

  • Jitendra R. Dave
  • Anthony J. Williams
  • John R. Moffett
  • Michael L. Koenig
  • Frank C. Tortella


While the role of apoptosis in neuronal injury is continually being re-defined, approaches to intervene in the progression of apoptotic injury have been documented to provide neuroprotection against a variety of insults. The present studies were undertaken to systematically study the effects of certain neuroprotective agents against neuronal apoptosis mediated by staurosporine (ST). ST (0.01–5 μM) produced a dose-related apoptotic injury (as characterized by cellular morphology, ‘Comet’ assay analysis [single cell gel electrophoresis] and caspase-3 activation) in primary cultures of forebrain neurons. ST significantly increased caspase-3 activity. The NMDA receptor subtype non-selective antagonist dizocilpine [(+) MK-801; 0.1–50 μM) and a novel sodium channel blocker RS100642 (1.0–250 μM) had no significant effects against ST-induced neurotoxicity. Conversely, NR2B-selective NMDA receptor antagonists CGX-1007 (0.01–50 μM) and ifenprodil (0.01–50 μM) provided dose-dependent neuroprotection against ST-induced neurotoxicity (as measured by neuronal viability and comet assay analysis). CGX-1007 had no significant effect on ST-induced caspase-3 activity; however, ifenprodil did block activation of caspase-3. These studies demonstrate that NR2B NMDA receptor antagonists are anti-apoptotic and may mediate their action via mechanism(s) that are dependent or independent of caspase-3 activation.


Primary neuronal cultures Apoptosis Staurosporine Ifenprodil CGX-1007 Conantokin-G 


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Copyright information

© FP Graham Publishing Co 2003

Authors and Affiliations

  • Jitendra R. Dave
    • 1
  • Anthony J. Williams
    • 1
  • John R. Moffett
    • 1
  • Michael L. Koenig
    • 2
  • Frank C. Tortella
    • 1
  1. 1.Department of Neuropharmacology and Molecular Biology, Division of NeurosciencesWalter Reed Army Institute of RearchSilver SpringUSA
  2. 2.Department of Neuroendocrinology/Neurochemistry, Division of NeurosciencesWalter Reed Army Institute of ResearchSilver SpringUSA

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