The distribution of β-amyloid precursor protein in rat cortex after systemic kainate-induced seizures

In the current study we employed immunohistochemical techniques to identify neuronal and glial cells in specific brain areas that modulate β- amyloid precursor protein (β-APP) synthesis following kainate-induced seizures. In addition, antibodies directed against the FOS protein, which is generated by activation of the immediate early gene c-fos and is temporally associated with ongoing seizure activity, were used to identify transneuronal pathways activated after kainate-induced seizures (KIS). It was therefore possible to correlate the appearance of activated neuronal pathways identified by FOS-like immunoreactivity (LI) and βAPP-LI in alternate sections. In addition, we employed immunohistochemical procedures to characterize morphological changes in neuronal and glial cells following kainate-induced seizures in both young and adult rats. Our results demonstrate a specific pattern of FOS-LI induced by kainate injection. In older animals FOS-LI spreads out from limbic cortical regions, including the piriform and entorhinal cortex, to other cortical regions, including the parietal and somatosensory cortices. Seizures were associated with decrease in neuronal βAPP-LI in both young and adult rats, whereas glial βAPP-LI markedly increased. The increase in βAPP-LI glia was far more extensive in adult than in young rats and the anatomical distribution of βAPP-LI gila was grossly correlated with FOSLI. The spread of βAPP-LI follows seizure- activated transsynaptic pathways. It is likely that the sequence of events following kainate injection is initially triggered by c-fos gene expression, which is rapidly followed by modulation of βAPP synthesis in parallel to, or preceding, morphological changes of both microglia and astrocytes. The present study, which extensively characterized early changes in c-fos expression and βAPP-LI in glia following kainate-induced seizures, is a potentially useful animal model for the in vivo study of numerous facets of βAPP synthesis and the possible role of such processes in Alzheimer's disease.