Developmental changes in transporter and receptor protein expression levels at the rat blood-brain barrier based on quantitative targeted absolute proteomics

Abstract

The blood-brain barrier (BBB) transport systems regulate the supply of nutrients, amino acids, vitamins, and hormones to the developing brain, as well as blocking the entry of xenobiotics and drugs. The purpose of this study was to clarify the developmental changes in the absolute protein expression levels of BBB transport-related proteins in developing rat brain capillaries, using quantitative targeted absolute proteomics (QTAP). The changing patterns of ATP-binding cassette (ABC) and solute carrier (SLC) transporters, receptors, and tight junction/adherence junction-related proteins were classified into 4 types: uphill (continuously increasing expression from postnatal day (P) 1 to P56), bell-shape/inverted bell-shape (increased/decreased expression from P1 to P14 followed by decreased/increased expression from P21 to P56), downhill (continuously decreasing expression from P1 to P56), and constant (no significant difference from P1 to P56). Proteins showing uphill-type expression included P-glycoprotein/Mdr1a/Abcb1, Mrp4/Abcc4, Bcrp/Abcg2, Glut1/Slc2a1, Oatp1c1/Slco1c1, FcRn, 4F2hc/Slc3a2, claudin-5, caveolin-1, Cd29/integrin β1. Those showing bell-shape/inverted bell-shape expression included Mct1/Slc16a1, Oat3/Slc22a8, Tfr1, Lrp1, and CD147. On the other hand, Cat1/Slc7a1 and Cd54/Icam-1 showed downhill expression, and Insr showed constant expression. These results suggest that the protein expression levels of transporters and receptors at the BBB change in various ways to meet the changing requirements of the developing brain.