Loss of the p53 tumor suppressor gene protects neurons from kainate- induced cell death

摘要: The tumor suppressor gene p53 recently has been associated with the induction of cell death in response to some forms cellular damage. A possible role for p53-related modulation neuronal viability suggested by finding that expression is increased damaged neurons models ischemia and epilepsy. We evaluated possibility (in knockout mice) required damage a model seizure activity normally well defined patterns loss. Subcutaneous injection kainic acid, potent excitotoxin, induced comparable seizures both wild-type mice (+/+) deficient (-/-). Using silver impregnation technique examine neurodegeneration animals killed 7 d after kainate injection, we found majority +/+ exhibited extensive loss hippocampus, involving subregions CA1, CA3, hilus, subiculum. Apoptotic death, as identified an situ nick end labeling detect DNA fragmentation, was confirmed CA1- but not CA3- degenerating neurons. In marked contrast, -/- displayed no signs damage; remaining mice, mild moderate confined almost entirely cells CA3b dorsal hippocampus. also were observed amygdala, piriform cortex, cerebral caudate-putamen, thalamus treatment. pattern extent heterozygous (+/-) identical those seen suggesting single copy sufficient confer vulnerability. These results demonstrate influences multiple subtypes brain regions excitotoxic insult.