Distribution of divalent metal transporter 1 and metal transport protein 1in the normal and Belgrade rat

Iron accumulation in the brain occurs in a number of neurodegenerative dise ases. Two new iron transport proteins have been identified that may help el ucidate the mechanism of abnormal iron accumulation. The Divalent Metal Tra nsporter 1 (DMT1), is responsible for iron uptake from the gut and transpor t from endosomes. The Metal Transport Protein 1 (MTP1) promotes iron export . In this study we determined the cellular and regional expression of these two transporters in the brains of normal adult and Belgrade rats. Belgrade rats have a defect in DMT1 that is associated with lower levels of iron in the brain. In the normal rat, DMT1 expression is highest in neurons in the striatum, cerebellum, thalamus, ependymal cells lining the third ventricle , and vascular cells throughout the brain. The staining in the ependymal ce lls and endothelial cells suggests that DMT1 has an important role in iron transport into the brain. In Belgrade rats, there is generalized decrease i n immunodetectable DMT1 compared to normal rats except in the ependymal cel ls. This decrease in immunoreactivity, however, was absent on immunoblots. The immunoblot analysis indicates that this protein did not upregulate to c ompensate for the chronic defect in iron transport. MTP1 staining is found in most brain regions. MTP1 expression in the brain is robust in pyramidal neurons of the cerebral cortex but is not detected in the vascular endothel ial cells and ependymal cells. MTP1 staining in Belgrade rats was decreased compared to normal, but similar to DMT1 this decrease was not corroborated by immunoblotting. These results indicate that DMT1 and MT are involved in brain iron transport and this involvement is regionally and cellularly spe cific. (C) 2001 Wiley-Liss, Inc.