DO C-JUN, C-FOS, AND AMYLOID PRECURSOR PROTEIN PLAY A ROLE IN NEURONAL DEATH OR SURVIVAL

A unilateral hypoxic-ischemic (HI) episode in immature rat brain was u sed to investigate the role of the immediate early genes c-fos and c-j un in delayed neuronal death and survival, This HI paradigm results in an apoptotic cell death in selectively vulnerable areas, in particula r the hippocampal CA1 pyramidal cell layer. In susceptible regions und ergoing delayed neuronal death there was a prolonged induction of both c-Jun and c-Fos (mRNA and protein). This expression occurred in paral lel with a pronounced increase in AP-1 DNA binding activity but was no t associated with either increased levels of Jun NH2-terminal kinase o r phosphorylation of c-Jun (ser-63), In addition to changes in immedia te early gene expression, the CA1 neurons showed a delayed increase in the expression of amyloid precursor protein (APP(751)) mRNA, suggesti ng that APP, which contains an AP-1 site, might be a down-stream gene regulated by the Jun transcription factor in neurons dying by apoptosi s. The surviving dentate granule cells also showed an increase in Fos, Jun, and APP(751) although this expression occurred earlier than in t he CA1 neurons and declined rapidly, These results are discussed with respect to the role of these proteins in neuronal death and survival. J, Neurosci. Res. 53:330-332, 1998, (C) 1998 Wiley-Liss, Inc.