SELECTIVE C-JUN EXPRESSION IN CA1 NEURONS OF THE GERBIL HIPPOCAMPUS DURING AND AFTER ACQUISITION OF AN ISCHEMIA-TOLERANT STATE

The selective delayed neuronal death of CA1 pyramidal cells after tran sient global ischemia in the gerbil brain can be prevented by precondi tioning with a short sublethal period of ischemia 1 - 7 days prior to a subsequent, usually lethal ischemia of 5 min duration. Since changes of neuronal gene expression may play a crucial role in this tolerance induction, we investigated the postischemic expression profile of the fos, jun and Krox transcription factor families. We have previously r eported that a single 5 min period of cerebral ischemia does not cause a de novo synthesis of immediate early gene (IEG) encoded proteins in CA1 neurons. In the present study, two experimental groups of Mongoli an gerbils were investigated: one group was subjected to a single tole rance-inducing 2.5 min period of ischemia by bilateral occlusion of th e common carotid artery. The second (combined ischemia) group was subj ected to 2.5 min of ischemia, followed by 5 min of ischemia 4 days lat er. Postischemic expression of c-FOS, FOS B, c-JUN, JUN B, JUN D and K ROX-24 was investigated by in situ hybridization and immunocytochemist ry up to 48 h of recirculation. In contrast to a single 5 min period o f ischemia, 2.5 min caused a postischemic expression of c-JUN protein, but no other IEGs, in CA1 neurons (peak at 6 h). Similarly, a selecti ve but delayed c-JUN expression (peak at 18 h) was observed in animals subjected to combined ischemia. These results indicate that the induc tion of an endogenous neuroprotective state in CA1 neurons is associat ed with the activation of a genetic program which involves the express ion of specific transcription factors.