Wnt/B-Catenin signaling control regulation of ABSG2 and OATP1A4 but not ABCB1 at the blood-brain barrier during brain development
Abstract
A number of transport and carrier systems are expressed and polarized on the luminal or abluminal surface of the blood-brain barrier (BBB). Among these systems, ABC transporters and SLC membrane transporting proteins, control cellular uptake and efflux of nutrients, neurotransmitters, metabolites, toxins, and therapeutics compounds. Despite their importance, the current knowledge about these drug transporters in the developing brain is very limited. Whether these components are regulated differently during development remains unclear. Because intricate developmental processes are taking place during the prenatal and postnatal periods we hypothesized that BBB transporters undergo substantial and rapid changes in expression and activity during ontogenesis. ln this study we examined gene expression of a series of ABC and SLC efflux transporters in cerebral microvessels from new born, child and adult rats. Most of the analyzed genes showed varied gene expression pattern as the brain matures, with some notable exceptions. Moreover, we provide evidence on the role of WnUI3-Catenin signaling in the regulation of ABCG2 and OATP1A4 but not ABCB1 at the BBB during brain development. These data shed light on BB.B changing properties during ontogenesis and serve as a necessary base for further studies on the regulation of ABC and SLC transporters in developing brain.