HIPPOCAMPAL MYC AND P53 EXPRESSION FOLLOWING TRANSIENT GLOBAL-ISCHEMIA

The proto-oncogene c-myc, and the tumor suppressor gene p53, encode pr oteins which function as transcriptional regulating factors governing cell proliferation, differentiation, and apoptosis. Recent evidence su ggests that the delayed neuronal death which follows an episode of tra nsient forebrain ischemia may involve apoptotic processes. We have the refore utilized immunohistochemistry to investigate the effects of tra nsient global ischemia on neuronal expression of p53- and Myc-like imm unoreactivities in the rodent forebrain 2, 12, 24, 48, and 72 h follow ing reperfusion. Transient global ischemia (20 min), produced by four vessel occlusion (4-VO), initially elevated p53-like immunoreactivity in both CA1 and CA3 hippocampal subfields at 24 h of recirculation. Ho wever, distinct patterns of gene expression became evident in these re gions at later time points. A pivotal difference was the persistence o f ischemia-induced increases of p53- and Myc-like immunoreactivity in the CA1 region of the hippocampus. Unlike CA3 neurons where p53-like i mmunoreactivity subsided to basal levels by 48 h of survival, CA1 neur ons continued to display increased p53-immunoreactivity 48 h post-isch emia, while Myc-like immunoreactivity was selectively elevated in CA1 neurons at this time point. Ischemia-induced increases in p53-like imm unoreactivity were also detected in vulnerable regions of the amygdala , thalamus, and cortex 12 to 48 h after recirculation. Given that both p53 and Myc have been implicated in gene signalling pathways which me diate programmed cell death, our findings which demonstrate that 4-VO produces persistent elevations of p53- and Myc-like immunoreactivities in vulnerable neurons suggest that these proteins may also contribute to delayed neuronal death following an episode of transient forebrain ischemia. (C) 1998 Elsevier Science B.V.