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

Abstract

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 labelling (TUNEL) reaction, selectively appeared in the CA1 region of the pyramidal cell layer between the third and fourth days after the insult. Concomitantly, an enhanced immunoreactivity to anti-cJun/AP1 (N) antibody as a major component of activator protein 1 (AP1) transcriptional factor was observed in CA1 neurons. In contrast, in the early postischemic phase, the cJun/AP1 reaction was noticed in numerous neurons and glia-like cells of the CA2/CA3 region, hilus of the dentate gyrus, and region of mossy fiber terminals. In parallel, hippocampal protein binding to AP1, measured by the electrophoretic mobility shift assay (EMSA), showed biphasic enhancement at 3 and then 72-120 hours after ischemia. Supershifts, with antibodies against c-Fos and phospho-c-Jun constituencies of the AP1 dimer, revealed an increased amount of phosphorylated c-Jun in the late postischemic phase. Collectively, these results suggest diversity of AP1 complex function, regulated by its dimer composition as well as time and place of expression during postischemic reperfusion. The early, survival-supporting AP1 response, located mainly in ischemia-resistant areas of CA2/3, is followed by the delayed phase, characteristic of massive neuronal apoptosis in CA1 with concomitant increase of phospho-c-Jun in AP1 dimer.

Pattern of Transcription Factor Activation in Helicobacter pylori–Infected Mongolian Gerbils

“…A few prior studies have investigated the roles of transcription factors (AP-1 and NF-κB) in gerbils with brain damage. [29][30][31][32] This study focused on effects of H pylori infection on transcription factors in the gastric mucosa of gerbils. We also used DNA/protein arrays for 54 different transcription factors, based on the premise that consensus transcription factor binding sites are conserved among species.…”

The Potential Role of Metalloproteinases in Neurogenesis in the Gerbil Hippocampus Following Global Forebrain Ischemia

“…The animals were allowed free access to food and water. Forebrain ischemia was performed as described previously [22] by 5-minute bilateral ligation of the common carotid arteries under halothane/N 2 O anesthesia in strictly controlled normothermic conditions. Sham-operated gerbils served as controls.…”

Comparative analysis of cis-regulation following stroke and seizures in subspaces of conserved eigensystems

“…Activation of transcription factor AP1 following the kainate-induced seizures and cerebral ischemia is well established [32,33]. In particular, Timp1 was shown to be the target of AP1 following kainate-induced seizures [34].…”