title: Acute, but reversible, kainic acid-induced DNA damage in hippocampal CA1 pyramidal cells of p53-deficient mice.
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.
authors.affiliation: Department of Neurological Surgery, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: H Jürgen
authors.initials: HJ
authors.lastname: Wenzel
authors.forename: Chizuru
authors.initials: C
authors.lastname: Kinoshita
authors.forename: Philip A
authors.initials: PA
authors.lastname: Schwartzkroin
authors.forename: Richard S
authors.initials: RS
authors.lastname: Morrison
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D002452:Cell Count; D002470:Cell Survival; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005260:Female; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010477:Perfusion; D011247:Pregnancy; D017966:Pyramidal Cells / Q000473:pathology*; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D018690:Excitatory Amino Acid Agonists; D016159:Tumor Suppressor Protein p53; D007608:Kainic Acid