Tumor suppressor p53 induction and DNA damage in hippocampal granule cells after adrenalectomy.

Tumor suppressor p53 encodes a protein that is an important regulator of the cell cycle. However, under certain conditions increased p53 expression results in programmed cell death or apoptosis. We used in situ hybridization histochemistry to investigate the role of p53 in the adrenalectomy-induced degeneration of hippocampal granule cells. Three days after adrenalectomy, a subpopulation of granule cells exhibiting morphological features of apoptosis expressed increased amounts of p53 mRNA. Both adrenalectomy-induced p53 expression and granule cell degeneration were prevented by daily administration of corticosterone. In situ end-labeling of nuclei containing fragmented DNA revealed a distribution similar to that of cells with increased p53 expression. These results demonstrate an association between p53 induction and apoptosis in the central nervous system and support the idea that cell cycle-related genes play a role in neuronal death pathways.