Cellular distribution of ferric iron, ferritin, transferrin and divalent metal transporter 1 (DMT1) in substantia nigra and basal ganglia of normal and beta2-microglobulin deficient mouse brain.
We examined whether high levels of circulatory iron may cause iron accumulation in the brain. In particular, we focussed on the substantia nigra and basal ganglia as several papers have indicated that iron may accumulate here and cause death of dopaminergic neurons. Normal mice and a mouse model of hereditary haemochromatosis, the beta2-microglobulin (beta2m) knock out [beta2m (-/-)] mouse, which has high levels of circulating iron due to increased iron absorption, were examined. The iron concentration in livers were: 170+/-15 microg/g (mean +/- SD) in controls and 1010+/-50 microg/g in beta2m (-/-) mice (p<0.001), whereas in the brain the respective values were 47 +/-1 microg/g and 53+/-2 microg/g (p<0.02). Hence, the difference between cerebral iron levels of normal and beta2m (-/-) mice was small. Histological examination of the brains revealed an unequivocal distribution of ferric iron, ferritin, transferrin and divalent metal transporter 1 (DMT1), which were indistinguishable when normal and beta2m (-/-) mice were compared. In the substantia nigra and basal ganglia, ferric iron and the iron-binding proteins were present in identical cell types, which mainly comprised oligodendrocytes and microglia. Neurons were lightly labelled with transferrin and DMT1. The virtual lack of an increase in cerebral iron in beta2m (-/-) mice clearly shows that the blood-brain barrier (BBB) is capable of restricting the transport of excess plasma iron into the brain.
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Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Denmark. T.Moos@mai.ku.dk
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D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins; D004195:Disease Models, Animal; D005290:Ferric Compounds / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism*; D006432:Hemochromatosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011817:Rabbits; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D014168:Transferrin / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics; D000099236:Solute Carrier Family 11, Member 2
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D005290:Ferric Compounds; D005293:Ferritins; D007501:Iron; D033862:Iron-Binding Proteins; D014168:Transferrin; D001613:beta 2-Microglobulin; D000099236:Solute Carrier Family 11, Member 2