Influence of transferrin on manganese uptake in rat brain

To evaluate the influence of transferrin (Tf) on manganese (Mn) uptake in the brain, pH 8.6 buffer-treated (54)MnCl(2), which has a higher affinity for Tf than untreated (54)MnCl(2), and Tf-bound (54)Mn were prepared. When pH 8.6 buffer-treated (54)MnCl(2) and untreated (54)MnCl(2) were incubated with apo-Tf in Tris (2-amino-2-hydroxymethylpropane-1,3-diol)-HCl buffer, the percentage of the total (54)MnCl(2) bound to Tf was approximately 85% and 10%, respectively. One hour after intravenous (iv) injection of pH 8.6 buffer-treated (54)MnCl(2) and untreated (54)MnCl(2), both tracers were concentrated similarly in the choroid plexus in the ventricles and distributed in other brain regions. Six days after iv injection, both pH 8.6 buffer-treated (54)MnCl(2) and untreated (54)MnCl(2) tracers were concentrated in the superior olivary complex, inferior colliculi, and red nuclei, although the former radioactivity was lower than the latter. Moreover, Tf-bound (54)Mn was prepared and injected iv into rats. The radioactivity from Tf-bound (54)Mn, which was also concentrated in the same regions, e.g., the superior olivary complex, was the lowest of all three traces. Tf-bound (54)Mn was stable during incubation with serum for 1 hr. It is likely that more Mn is transported into the brain when Mn is not bound to Tf. When Tf-bound (54)Mn and (54)MnCl(2) were unilaterally injected into the lateral ventricle, radioactivity was distributed only around the ipsilateral ventricle in the Tf-bound (54)Mn group 7 days after injection, whereas it was distributed more extensively in the (54)MnCl(2) group. It is likely that Tf-bound Mn in the CSF is less readily transported into the brain parenchymal cells than the non-Tf-bound form. These results suggest that Mn is transported into the brain efficiently via a Tf-independent uptake system.