Induction of tumor suppressor p53 and DNA fragmentation in organotypic hippocampal cultures following excitotoxin treatment

Exp Neurol. 1997 May;145(1):81-8. doi: 10.1006/exnr.1997.6451.


The p53 tumor suppressor gene encodes a cell cycle regulatory protein that is induced by DNA damage and has been implicated in apoptosis. To investigate whether excitotoxic cell death due to kainic acid (KA) and cell death due to N-methyl-D-aspartate (NMDA) share similar molecular mechanisms, we studied p53 expression and DNA fragmentation in organotypic hippocampal slice cultures following excitotoxin treatment. Cellular analyses showed that both p53 induction and DNA fragmentation occurred only in injured neurons following exposure to either excitotoxin. The temporal profiles of these changes demonstrated that p53 induction preceded DNA fragmentation. The extent of regional alterations in p53 expression and DNA fragmentation correlated with drug-related toxicity (i.e., NMDA > KA). These results support the hypothesis that p53 is a marker of neuronal death in the CNS and suggest the possibility that excitotoxin-mediated neuronal death may occur through a p53-dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Cell Death / drug effects
  • Cell Death / physiology
  • DNA Fragmentation / drug effects
  • DNA Fragmentation / physiology*
  • Dentate Gyrus / chemistry
  • Dentate Gyrus / metabolism*
  • Excitatory Amino Acid Agonists / pharmacology
  • Gene Expression Regulation / drug effects
  • In Situ Hybridization
  • Kainic Acid / pharmacology
  • Mammals
  • N-Methylaspartate / pharmacology
  • Neurotoxins / pharmacology*
  • Organ Culture Techniques
  • Pyramidal Cells / chemistry
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • RNA, Messenger / metabolism
  • Time Factors
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism


  • Excitatory Amino Acid Agonists
  • Neurotoxins
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • N-Methylaspartate
  • Kainic Acid