COEXPRESSION OF C-FOS AND HSP70 MESSENGER-RNA IN GERBIL BRAIN AFTER ISCHEMIA - INDUCTION THRESHOLD, DISTRIBUTION AND TIME-COURSE EVALUATED BY IN-SITU HYBRIDIZATION

Levels of mRNAs encoding the proto-oncogene, c-fos, and the 70 kDa str ess protein, hsp70, were evaluated in gerbil brain following transient cerebral ischemia of varied duration by in situ and blot hybridizatio n techniques. Blots of total hippocampal RNA obtained after 5 min isch emic insults confirmed a characteristic, transient time course of c-fo s expression with a striking elevation within 1 h and a return to cont rol levels by 3 h recirculation. Hsp70 hybridization was significant a t 1 h and continued to increase until 3-6 h after the insult. Striking accumulation of c-fos mRNA was detected within 15 min recirculation i n dentate granule cells, persisting through 1 h, and a weaker signal w as evident in CA1 and CA3 pyramidal neurons of hippocampus, as well as in prepiriform/entorhinal cortex and neocortical regions, during the same interval. Hsp70 hybridization showed an identical distribution at 1 h recirculation. Ischemic insults of 1 min duration resulted in no detectable increase of either mRNA, while 2 min ischemia resulted in c hanges comparable to those seen after 5 min insults. This common thres hold corresponds to the ischemic interval required for energy depletio n and resultant failure of intracellular ion homeostasis. In contrast, expression of hsp70 mRNA was not observed under conditions of brief d epolarization accompanying cortical or hippocampal spreading depressio n that were shown to induce c-fos. A delayed component of c-fos mRNA e xpression was not detected in this model, while persistent hsp70 hybri dization, restricted to hippocampal CA1 neurons, was evident at 48 h a fter either 2 min or 5 min ischemic insults. The parallels in c-fos an d hsp70 mRNA expression during early recirculation suggest that overla pping mechanisms triggered following postischemic depolarization contr ibute to their induction after transient ischemia.