X-RAY-INDUCED CELL-DEATH IN THE DEVELOPING HIPPOCAMPAL COMPLEX INVOLVES NEURONS AND REQUIRES PROTEIN-SYNTHESIS

Sprague-Dawley rats aged 1 or 15 days were irradiated with a single do se of 200 cGy X-rays and killed at different intervals from 3 to 48 ho urs (h). Dying cells were recognized by their shrunken and often fragm ented nuclei and less damaged cytoplasm in the early stages. On the ba sis of immunocytochemical markers, dying cells probably represented a heterogeneous population which included neurons and immature cells. In rats aged 1 day the number of dying cells rapidly increased in the hi ppocampal complex with peak values 6 h after irradiation. This was fol lowed by a gentle decrease to reach normal values 48 h after irradiati on. The most severely affected regions were the subplate and the cellu lar layer of the subiculum, gyrus dentatus and hilus, and the stratum oriens and pyramidale of the hippocampus (CA1 more affected than CA2, and this more affected than CA3). X-ray-induced cell death was abolish ed with an injection of cycloheximide (2 mu/g i.p.) given at the time of irradiation. X-ray-induced cell death was not changed after the int raventricular administration of nerve growth factor (NGF; 10 mug in sa line) at the time of irradiation. Cell death was not induced by X-irra diation in rats aged 15 days. These results indicate that X-ray-induce d cell death in the hippocampal complex of the developing rat is subje cted to determinate temporal and regional patterns of vulnerability; i t is an active process mediated by protein synthesis but probably not dependent on NGF.