Acute, but reversible, kainic acid-induced DNA damage in hippocampal CA1 pyramidal cells of p53-deficient mice

Yoshito Kinoshita, H. Jürgen Wenzel, Chizuru Kinoshita, Philip A Schwartzkroin, Richard S. Morrison

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

p53 plays an essential role in mediating apoptotic responses to cellular stress, especially DNA damage. In a kainic acid (KA)-induced seizure model in mice, hippocampal CA1 pyramidal cells undergo delayed neuronal death at day 3-4 following systemic KA administration. We previously demonstrated that CA1 neurons in p53 -/- animals are protected from such apoptotic neuronal loss. However, extensive morphological damage associated with DNA strand breaks in CA1 neurons was found in a fraction of p53 -/- animals at earlier time points (8 h to 2 days). No comparable acute damage was observed in wild-type animals. Stereological counting confirmed that there was no significant loss of CA1 pyramidal cells in p53 -/- animals at 7 days post-KA injection. These results suggest that seizure-induced DNA strand breaks are accumulated to a greater extent but do not lead to apoptosis in the absence of p53. In wild-type animals, therefore, p53 appears to stimulate DNA repair and also mediate apoptosis in CA1 neurons in this excitotoxicity model. These results also reflect remarkable plasticity of neurons in recovery from injury.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalEpilepsia
Volume53
Issue numberSUPPL. 1
DOIs
StatePublished - Jun 2012

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Pyramidal Cells
Kainic Acid
DNA Damage
Neurons
DNA Breaks
Wild Animals
Seizures
Apoptosis
DNA Repair
Injections
Wounds and Injuries

Keywords

  • Apoptosis
  • Excitotoxicity
  • Neuronal cell death
  • Seizure

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Acute, but reversible, kainic acid-induced DNA damage in hippocampal CA1 pyramidal cells of p53-deficient mice. / Kinoshita, Yoshito; Jürgen Wenzel, H.; Kinoshita, Chizuru; Schwartzkroin, Philip A; Morrison, Richard S.

In: Epilepsia, Vol. 53, No. SUPPL. 1, 06.2012, p. 125-133.

Research output: Contribution to journalArticle

Kinoshita, Yoshito ; Jürgen Wenzel, H. ; Kinoshita, Chizuru ; Schwartzkroin, Philip A ; Morrison, Richard S. / Acute, but reversible, kainic acid-induced DNA damage in hippocampal CA1 pyramidal cells of p53-deficient mice. In: Epilepsia. 2012 ; Vol. 53, No. SUPPL. 1. pp. 125-133.
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