Altered expression of iron‐management proteins in the brain microvasculature of Restless Legs Syndrome

Restless Legs Syndrome (RLS) is a common movement related sleep disorder affecting 5–10% of the general population. Although the pathogenesis of RLS is still unclear, MRI, postmortem brain tissue and CSF analyses consistently indicate that brain iron insufficiency is associated with RLS. Given the consistent evidence of insufficient brain iron in RLS, we hypothesized that the profile of iron management proteins in the brain microvasculature would be altered in RLS. To test the hypothesis, microvessels were isolated from the temporal cortex of five RLS and five control brains. The concentrations of H ferritin, L ferritin, mitochondrial ferritin, transferrin receptor (TfR), transferrin, divalent metal transporter 1, ferroportin, and prohepcidin were determined by immunoblot assay. Our results reveal a significant decrease in the expression of HFRT in the microvessels from RLS compared to the controls indicating that there is low iron status in the endothelial cells of the blood brain barrier (BBB). There was also a significant decrease in the expression of transferrin and TfR in the microvasculature from the RLS brains. Normally, when a cell is iron deficient, TfR are elevated. The data are consistent with our position that there is a misregulation of TfR expression in RLS and imply that brain iron deficiency in RLS could begin at the level of transport across BBB.