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Acute, but reversible, kainic acid–induced DNA damage in hippocampal CA1 pyramidal cells of p53‐deficient mice
Author(s) -
Kinoshita Yoshito,
Jürgen Wenzel H.,
Kinoshita Chizuru,
Schwartzkroin Philip A.,
Morrison Richard S.
Publication year - 2012
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2012.03483.x
Subject(s) - kainic acid , hippocampal formation , dna damage , apoptosis , excitotoxicity , biology , programmed cell death , hippocampus , pyramidal cell , microbiology and biotechnology , neuroscience , chemistry , dna , biochemistry , glutamate receptor , receptor
Summary 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.