CELL CYCLE-RELATED GENE-EXPRESSION IN THE ADULT-RAT BRAIN - SELECTIVEINDUCTION OF CYCLIN G1 AND P21(WAF1 CIP1) IN NEURONS FOLLOWING FOCAL CEREBRAL-ISCHEMIA/

The present studies were initiated to investigate whether p53 transact ivated target genes are induced in a rat model of focal cerebral ische mia. Therefore, we applied in situ hybridization, immunocytochemistry and western blotting to study the temporal and spatial expression of p 53 and its transcriptional targets Bax, p21 and cyclin G1 following pe rmanent middle cerebral artery occlusion in the rat. Cyclin G1 immunor eactivity was constitutively expressed in the nuclei of cells in the c horoid plexus and ependymal cell layer and in the cytoplasm of cell bo dies and dendrites of pyramidal neurons of the cerebral cortex. Cyclin G1 messenger RNA and protein levels transiently increased to 150% of contralateral levels in neurons of the ipsilateral frontal and parieta l cortex and striatum 3 h following middle cerebral artery occlusion. A low level of constitutively expressed p21 messenger RNA and protein was found in nuclei of cells in the choroid plexus, oligodendrocytes a nd neurons. p21 messenger RNA and protein levels gradually increased t o 250% and 140% of contralateral levels in areas bordering the infarct core up to 6 h following middle cerebral artery occlusion. In contras t, p53 and Bax messenger RNA and protein levels, and protein levels of p27, cyclin-dependent kinase 5, p35 and cyclin E decreased in the inf arct core and border areas with rime after middle cerebral artery occl usion. The selective up-regulation of cyclin G1 and p21 in neurons in the border zone of a focal ischemic infarct indicates their involvemen t in an adaptive response to ischemic injury. The possible participati on of cyclin G1 and p21 in a signal transduction pathway associated wi th ischemia-induced cellular stress is discussed. (C) 1998 IBRO. Publi shed by Elsevier Science Ltd.