Transferrin and Iron Uptake by the Brain: Effects of Altered Iron Status

Abstract

: Transferrin (Tf) and iron uptake by the brain were measured in rats using ⁵⁹Fe-¹²⁵I-Tf and ¹³¹I-albumin (to correct for the plasma content of ⁵⁹Fe and ¹²⁵I-Tf in the organs). The rats were aged from 15 to 63 days and were fed (a) a low-iron diet (iron-deficient) or, as control, the same diet supplemented with iron, or (b) a chow diet with added carbonyl iron (iron overload), the chow diet alone acting as its control. Iron deficiency was associated with a significant decrease and iron overload with a significant increase in brain nonheme iron concentration relative to the controls, in each dietary treatment group, the uptake of Tf and iron by the brain decreased as the rats aged from 15 to 63 days. Both Tf and iron uptake were significantly greater in the iron-deficient rats than in their controls and lower in the iron-loaded rats than in the corresponding controls. Overall, iron deficiency produced about a doubling and iron overload a halving of the uptake values compared with the controls. In contrast to that in the brain, iron uptake by the femurs did not decrease with age and there was relatively little difference between the different dietary groups. ¹²⁵I-Tf uptake by the brains of the iron-deficient rats increased very rapidly after injection of the labelled proteins, within 15 min reaching a plateau level which was maintained for at least 6 h. The uptake of ⁵⁹Fe, however, increased rapidly for 1 h and then more slowly, and in terms of percentage of injected dose reached much higher values than did ¹²⁵I-Tf uptake. It is concluded that, after the age of 15 days in the rat, there is a decline in the rate of uptake of iron by the brain, probably attributable to a decrease in the number of Tf receptors on brain capillary endothelial cells, and that the expression of these receptors is highly responsive to the iron status of the animal.