Expression of beta-amyloid precursor protein mRNAs following transient focal ischaemia

beta-AMYLOID precursor protein (beta APP) can be alternatively processed to result in release of either neurotoxic amyloid beta-peptide, or secreted forms of beta APP, which might have a role in neuronal plasticity and survival. Four different forms of beta APP mRNAs have been described in rodents: APP(695), APP(714), APP(751) and APP(770). The two larger forms contain a Kunitz-type serine protease inhibitor domain (KPI). Since previous studies have shown increased APP immunoreactivity following brain ischaemia, we used in situ hybridization histochemistry to determine whether induction of any APP mRNA transcripts take place following focal brain ischaemia. While the hybridization signal of all APP isoforms in the infarct was lost 4-24 h following the insult, APP(770) mRNA was slightly upregulated in the ipsilateral cortex and striatum 3 days after 90 min ischaemia. At 7 days post-ischaemia APP(770) and APP(751) mRNAs were induced in the infarct core and in a thin perifocal zone. KPI-containing APP forms are differentially induced following focal brain ischaemia, possibly as a neuroprotective response to neuronal injury.