A light and electron microscopic study of divalent metal transporter-1 distribution in the rat hippocampus, after kainate-induced neuronal injury

An accumulation of iron occurs in the hippocampus of rats injected with kainate over time, but thus far whether this accumulation is associated with any changes in expression of iron transporters is not known. The present study was therefore carried out using an antibody to the divalent metal transporter-1 (DMT-1) and immunoblot and immunocytochemical analyses to elucidate possible changes in expression of the transporter in the rat hippocampus after kainate injections. A significant increase in density ratios of DMT-1/β-actin bands was observed in Western blots in the 1-week, 1-month, and 2-months post-kainate-injected hippocampus, compared to uninjected and 1-day post-kainate-injected hippocampus. The increase in DMT-1 protein was paralleled by an increase in DMT-1 immunoreactivity in astrocytes. Light staining for DMT-1 was observed in the uninjected, saline-injected, and 1-day post-kainate-injected rat hippocampus. In contrast, an upregulation of DMT-1 was observed in reactive glial cells at 1 week, 1 month, and 2 months post-kainate injection. Electron microscopy confirmed that the glial cells had morphological features of astrocytes. DMT-1 is a cellular iron transporter responsible for transport of metal ions from the plasma membrane to endosomes. The observation that DMT-1 is present on astrocytic end feet in contact with blood vessels suggests that these cells may be involved in uptake of iron from endothelial cells.