Differential induction of p53 in immature and adult rat brain following lithium-pilocarpine status epilepticus

Abstract

Activation of the tumor suppressor gene, p53, has been strongly implicated in selective neuronal cell death. This study investigated p53 expression in the immature and adult rat brain following status epilepticus induced by the administration of lithium-pilocarpine (LPSE). Both p53 mRNA and protein were examined in relation to neuronal degeneration using in situ hybridization and immunohistochemistry, respectively. Injured cells with eosinophilic cytoplasm with increased p53 mRNA were observed in hippocampal subfields, piriform cortex, amygdala and thalamus. p53 mRNA levels reached a peak by 8 h and returned to baseline by 24 h after the onset of LPSE. The magnitude of p53 mRNA induction was greatest in 21-day-old rats. In contrast to the cellular expression pattern of p53 mRNA, immunohistochemistry demonstrated that p53 protein was increased in all of the eosinophilic cells. Further, double-labeling studies revealed that p53 protein was elevated in neurons that were degenerating. This was supported by colocalization of activated caspase 3 in some cells with damaged DNA. These results provide additional evidence for a critical role for the p53 pathway in excitotoxic neuronal cell death due to status epilepticus.