GAP-43 mRNA and protein expression in the hippocampal and parahippocampal region during the course of epileptogenesis in rats.

Abstract

In order to reveal axonal rewiring in the hippocampal and parahippocampal regions after status epilepticus, we investigated the temporal evolution of growth-associated protein-43 (GAP-43) mRNA and protein expression in two rat models of mesial temporal lobe epilepsy (MTLE). Status epilepticus (SE) was induced by electrical stimulation of the angular bundle or by intraperitoneal kainic acid (KA) injections. Despite increased GAP-43 mRNA expression in dentate granule cells at 24 h after SE, GAP-43 protein expression in the inner molecular layer (IML) of the dentate gyrus decreased progressively after 24 h after SE in both models. Nevertheless robust mossy fiber sprouting (MFS) was evident in the IML of chronic epileptic rats. Remaining GAP-43 protein expression in the IML in chronic epileptic rats did not correlate with the extent of MFS, but with the number of surviving hilar neurons. In the parahippocampal region, GAP-43 mRNA expression was decreased in layer III of the medial entorhinal area (MEAIII) in parallel with extensive neuronal loss in this layer. There was a tendency of GAP-43 mRNA up-regulation in the presubiculum, a region that projects to MEAIII. With regard to this parahippocampal region, however, changes in GAP-43 mRNA expression were not followed by protein changes. The presence of the presynaptic protein GAP-43 in a neurodegenerated MEAIII indicates that fibers still project to this layer. Whether reorganization of fibers has occurred in this region after SE needs to be investigated with tools other than GAP-43.