POSITIVE CORRELATION BETWEEN PROLONGED POTENTIATION OF BINDING OF DOUBLE-STRANDED OLIGONUCLEOTIDE PROBE FOR THE TRANSCRIPTION FACTOR AP1 AND RESISTANCE TO TRANSIENT FOREBRAIN ISCHEMIA IN GERBIL HIPPOCAMPUS

Gel retardation electrophoresis revealed that binding of a radiolabell ed double-stranded oligonucleotide probe for the nuclear transcription factor activator protein-1 was markedly potentiated in the CA1 and CA 3 subfields and the dentate gyrus of the hippocampus of the gerbils wi th transient forebrain ischemia for 5 min, which is known to induce de layed death of pyramidal neurons exclusively in the CAI subfield. The potentiation was transient in the vulnerable CAI subfield, but persist ent up to 18 h in the resistant CA3 subfield and dentate gyrus. Howeve r, no significant alteration was detected in endogenous levels of cycl ic AMP response element binding protein phosphorylated at serine(133) in these three different hippocampal structures 3 h after the reperfus ion. On the other hand, hypothermia during ischemia which is known to protect the CAI subfield against ischemic damages, led to a prolonged elevation of the activator protein-1 binding up to 9 h after the reper fusion in this vulnerable subfield at least in part through expression of c-Fos protein. Moreover, activator protein-1 binding was significa ntly elevated in the CA1 subfield up to 12 h after forebrain ischemia for 2 min which is shown not to induce marked damages to the vulnerabl e subfield. These results suggest that prolonged elevation of DNA bind ing activity of activator protein-1 may be responsible for molecular m echanisms underlying the unique vulnerability and/or resistance of par ticular subfields to a transient ischemic insult in the gerbil hippoca mpus. (C) 1997 IBRO. Published by Elsevier Science Ltd.