Cell death in the normal developing brain, and following ionizing radiation, methyl-azoxymethanol acetate, and hypoxia-ischaemia in the rat

Naturally occurring (programmed) cell death in the developing brain has morphological characteristics of apoptosis and is associated with internucleosomal DNA fragmentation. Apoptosis also plays a role in cell death following hypoxia-ischaemia in the developing rat brain. Ionizing radiation-induced cell death in the brain of the young rat has morphological characteristics of apoptosis. is mediated by protein synthesis and is associated with internucleosomal UNA fragmentation. Methylazoxymethanol (MAM) acetate injection in the young rat produces apoptotic cell death in the external granule cell layer of the cerebellum. In addition, strong c-Jun immunore-activity is observed in apoptotic cells during normal development and following experimentally induced cell death. Moreover, c-Jun mRNA induction and de novo c-Jun protein synthesis, together with activation of c-Jun/AP-1, as revealed with gel mobility shift assay, occurs in irradiated animals. Western blotting of total brain homogenates shows a c-Jun-immunoreactive band at p39, which corresponds to the molecular weight of c-Jun. in control rats. However, a thick c-Jun-immunoreactive band at about p62, accompanied by a decrease of the p39 band, occurs in irradiated and MAM-treated rats. A thin band immediately above the thick p62 band, suggestive of c-Jun phosphorylation, is also observed in treated rats. Taken together, these observations indicate that c-Jun expression is associated with apoptotic cell death in the developing central nervous system.