AP1 transcriptional factor activation and its relation to apoptosis of hippocampal CA1 pyramidal neurons after transient ischemia in gerbils

The cellular processes with a potential to lead to delayed death of neurons following transient (5 min) ischemia in gerbil hippocampus were evaluated. Neuronal apoptosis, visualized by the terminal transferase dUTP nick-end l abelling (TUNEL) reaction, selectively appeared in the CA1 region of the py ramidal cell layer between the third and fourth days after the insult. Conc omitantly, an enhanced immunoreactivity to anti-cJun/AP1 (N) antibody as a major component of activator protein 1 (AP1) transcriptional factor was obs erved in CA1 neurons. In contrast, in the early postischemic phase, the cJu n/AP1 reaction was noticed in numerous neurons and glia-like cells of the C A2/CA3 region, hilus of the dentate gyrus, and region of mossy fiber termin als. In parallel, hippocampal protein binding to AP1, measured by the elect rophoretic mobility shift assay (EMSA), showed biphasic enhancement at 3 an d then 72-120 hours after ischemia. Supershifts, with antibodies against c- Fos and phospho-c-Jun constituencies of the AP1 dimer, revealed an increase d amount of phosphorylated c-Jun in the late postischemic phase. Collective ly, these results suggest diversity of AP1 complex function, regulated by i ts dimer composition as well as time and place of expression during postisc hemic reperfusion. The early, survival-supporting AP1 response, located mai nly in ischemia-resistant areas of CA2/3, is followed by the delayed phase, characteristic of massive neuronal apoptosis in CA1 with concomitant incre ase of phospho-c-Jun in AP1 dimer. (C) 1999 Wiley-Liss, Inc.