In this study, we investigated the cellular distribution of iron in the bra
in of Belgrade rats. These rats have a mutation in Divalent Metal Transport
er 1, which has been implicated in iron transport from endosomes. The Belgr
ade rats have iron-positive pyramidal neurons, but these are fewer in numbe
r and less intensely stained than in controls. In the white matter, iron is
normally present in patches of intensely iron-stained oligodendrocytes and
myelin, but there is dramatically less iron staining in the Belgrade rat.
Those oligodendrocytes that stained for iron did so strongly and were assoc
iated with blood vessels. Astrocytic iron staining was seen in the cerebral
cortex for both normal rats and Belgrade rats, but the iron-stained astroc
ytes were less numerous in the mutants. Iron staining in tanycytes, modifie
d astrocytes coursing from the third ventricle to the hypothalamus, was not
affected in the Belgrade rat, but was affected by diet.
The results of this study indicate that Divalent Metal Transporter 1 is imp
ortant to iron transport in the brain. Iron is essential in the brain for b
asic metabolic processes such as heme formation, neurotransmitter productio
n and ATP synthesis. Excess brain iron is associated with a number of commo
n neurodegenerative diseases. Consequently, elucidating the mechanisms of b
rain iron delivery is critical for understanding the role of iron in pathol
ogical conditions. (C) 1999 IBRO. Published by Elsevier Science Ltd.