ABC Transporter (P-gp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) Expression in the Developing Human CNS

Abstract

P-glycoprotein (P-gp/ABCB1), multidrug resistance associated protein 1 (MRP1/ABCC1), and breast cancer resistance protein (BCRP/ABCG2) are plasma membrane efflux pumps that limit the intracellular uptake and retention of numerous lipophilic, amphipathic xeno- and endobiotics. Little is known about the neonatal and developmental expression of P-gp/ABCB1, MRP1/ABCC1, and BCRP/ABCG2 in the human central nervous system (CNS), therefore post-mortem CNS tissue from infants born at 22 (0/7)-42 (0/7) weeks of gestation and adults was immunostained to determine their ontogeny and cellular localization. P-gp/ABCB1 immunostaining was observed in microvessel endothelial cells as early as 22 (0/7) weeks, increasing in prevalence and intensity with maturation, and later in gestation in large pyramidal neurons. MRP1/ABCC1 immunostaining was prominent early in the choroid plexus and ventricular ependyma, and noted later in large pyramidal neurons. BCRP/ABCG2 expression was limited to microvessel endothelial cells. P-gp/ABCB1, MRP1/ABCC1 and BCRP/ABCG2 in adult brain matched term newborn CNS but with more intense immunostaining. We conclude that P-gp/ABCB1, MRP1/ABCC1, and BCRP/ABCG2 are expressed in a developmental, cell specific, fashion in the human CNS. The complementary pattern of P-gp/ABCB1 and BCRP/ABCG2 at the blood-brain with MRP1/ABCC1 at the blood-CSF barriers may limit CNS uptake and retention of drugs and toxins in neonates.