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 exp ression results in programmed cell death or apoptosis. We used in situ hybridization histochemistry to investigate the role of p53 in the ad renalectomy-induced degeneration of hippocampal granule cells. Three d ays after adrenalectomy, a subpopulation of granule cells exhibiting m orphological features of apoptosis expressed increased amounts of p53 mRNA. Both adrenalectomy-induced p53 expression and granule cell degen eration were prevented by daily administration of corticosterone. In s itu end-labeling of nuclei containing fragmented DNA revealed a distri bution similar to that of cells with increased p53 expression. These r esults demonstrate an association between p53 induction and apoptosis in the central nervous system and support the idea that cell cycle-rel ated genes play a role in neuronal death pathways. (C) 1994 Academic P ress, Inc.