Distribution of ferritin in the rat hippocampus after kainate-induced neuronal injury

Abstract

A gradual increase in iron occurs in the lesioned hippocampus after neuronal injury induced by the excitotoxin kainate, and the present study was carried out to investigate whether this increase in iron might be associated with changes in expression of the iron binding protein, ferritin. An increase in ferritin immunoreactivity was observed in glial cells of the hippocampus, as early as three days after intracerebroventricular injections of kainate. The number of ferritin positive cells peaked four weeks after the kainate injection, and decreased eight and twelve weeks after injection. They were found to be mostly microglia and oligodendrocytes by double immunofluorescence labeling with glial markers. A number of ferritin-labeled endothelial cells were also observed via electron microscopy. The decline in ferritin immunoreactivity four weeks after the injection of kainate is accompanied by an increase in the number of ferric and ferrous iron positive cells in the lesioned tissue. A substantial non-overlap between ferritin and iron-containing cells was observed. In particular, spherical ferric or ferrous iron-laden cells in the degenerating hippocampus were unlabeled for ferritin for long time periods after the kainate injection. An increase in iron, together with a reduced expression of iron binding proteins such as ferritin at long time intervals after kainate lesions, could result in a relative decrease in ferritin-induced ferroxidase activity and the presence of some of the iron in the ferrous form. It is postulated that this may contribute to chronic neuronal injury, following acute kainate-induced neurodegeneration.