Manganese transport by rat brain endothelial (RBE4) cell-based transwell model in the presence of astrocyte conditioned media

Manganese (Mn), an essential nutrient, is neurotoxic at high levels and has been associated with the development of a parkinsonian syndrome termed manganism. Currently, the mechanisms responsible for transporting Mn across the blood-brain barrier (BBB) are unknown. By using rat brain endothelial 4 (RBE4) cell monolayers cultured in astrocyte-conditioned media (ACM), we examine the effects of temperature, energy, proton (pH), iron (Fe), and sodium (Na ⁺) dependence on Mn transport. Our results suggest that Mn transport is temperature, energy, and pH dependent, but not Fe or Na⁺ dependent. These data suggest that Mn transport across the BBB is an active process, but they also demonstrate that the presence of ACM in endothelial cell cultures decreases the permeability of these cells to Mn, reinforcing the use of ACM or astrocyte cocultures in studies examining metal transport across the BBB.