Effects of intracerebroventricular injection of iron dextran on the iron concentration and divalent metal transporter 1 expression in the caudate putamen and substantia nigra of rats.

The cellular localization of DMT1 and its functional characterization suggest that DMT1 may play an important role in the physiological brain iron transport. But the regulation of DMT1 expression by iron in the brain is still not clearly understood. In this study, both the contents of ferric and ferrous iron as well as DMT1 expression were evaluated in CPu and SN after ICV of 500 microg iron dextran/rat/day for 3 or 7 days. It was found that the iron levels in CPu and SN were not altered obviously until ICV for 7 days. Immunohistochemistry results indicated that the expression of DMT1 (-IRE) in CPu and SN was not altered significantly after 3 days of ICV. Whereas the expression of DMT1 (-IRE) decreased significantly after 7 days of ICV when ferrous iron was increased significantly. Contrary to that of DMT1 (-IRE) in the same regions, there were no significant alterations in DMT1 (+IRE) expression in CPu and SN in spite of the existence of the altered iron levels, compared with that of control groups. The results demonstrate that DMT1 (-IRE) expression was correlated probably with brain iron levels; especially, its regulation was correlated with ferrous iron (not ferric iron) in CPu and SN in adult rats, compared with those of saline-injected control rats. The effect of ferrous iron on the expression of DMT1 (-IRE) in the brain also suggests that it might play a major physiological role in brain iron uptake and transport, but further studies are needed to clarify these issues.