Alteration of MAP kinase pathways after transient forebrain ischemia

Extracellular regulated kinase (ERK) transduce growth factor signals while c-Jun NH(2)-terminal kinase (JNK) delivers stress signals into the nuclei f or regulation of gene expression. These signaling pathways were studied by laser-scanning confocal microcopy and Western blot analysis using phospho-s pecific antibodies on rat brains that were subjected to 15 minutes transien t forebrain ischemia followed by varied periods of reperfusion. Extracellul ar regulated kinase was activated at 30 minutes and 4 hours of reperfusion in the nuclei and dendrites of surviving dentate gyrus (DG) cells, but not in dying CA1 neurons after ischemia. Tyrosine phosphorylation of Trk kinase , an ERK upstream growth factor receptor, was elevated in the DG tissue, an d to a lesser extent in the CA1 region. In addition, phosphorylation of act ivating transcription factor-2 (ATF-2) and c-Jun was selectively increased in CA1 dying neurons during the late period of reperfusion. These findings suggested that the Trk-ERK signaling pathway might be neuroprotective for d entate granule cells. The activation of ATF-2 and c-Jun pathways in the lat e period of reperfusion in CA1 dying neurons might reflect damage signals i n these neurons. These results suggested that the lack of protective signal s acting in concert with the presence of damage signals in CA1 neurons afte r ischemia might contribute to delayed neuronal death after transient foreb rain ischemia.