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. J. Neurosci. Res. 59:542–552, 2000 © 2000 Wiley‐Liss, Inc.