CELLULAR MANAGEMENT OF IRON IN THE BRAIN

All organs including the brain contain iron, and the proteins involved in iron uptake (transferrin and transferrin receptor) and intracellul ar storage (ferritin). However, because the brain resides behind a bar rier and has a heterogeneous population of cells, there are aspects of its iron management that are unique. Iron management, the timely deli very of appropriate amounts of iron, is crucial to normal brain develo pment and function. Mismanagement of cellular iron can result not only in decreased metabolic activity but increased vulnerability to oxidat ive damage. There is regional specificity in cell deposition of iron a nd the iron regulatory proteins. However, the sequestration of iron in the brain seems primarily the responsibility of oligodendrocytes, as these cells contain most of the stainable iron in the brain. Transferr in, the iron-mobilizing protein, is also found predominantly in these cells. The transferrin receptor is abundantly expressed on blood vesse ls, large neurons in the cortex, striatum, and hippocampus, and is als o present on oligodendrocytes and astrocytes. Ferritin, the intracellu lar iron storage protein, consists of 2 subunits which are functionall y distinct, and we provide evidence in this report that the cellular d istribution of the ferritin subunits is also distinct. In addition, ch anges in the cellular distribution of iron and its associated regulato ry proteins occur in Alzheimer's disease. Neuritic plaques contain rel atively large amounts of stainable iron, and the surrounding cells rob ustly immunostain for ferritin and the transferrin receptor. Analysis of the cellular distribution of iron indicates the different levels of requirement of iron in the brain by different cell types and should u ltimately elucidate how cells acquire and maintain this essential comp onent of oxidative metabolism. In addition, changes in the ability of cells to deliver and manage iron may provide insight into altered meta bolic activity with age and disease as well as identify cell populatio ns at risk for iron-induced oxidative stress.