title: Ontogeny of ABC and SLC transporters in the microvessels of developing rat brain.
abstract: The blood-brain barrier (BBB) is responsible for the control of solutes' concentration in the brain. Tight junctions and multiple ATP-binding cassette (ABC) and SoLute Carrier (SLC) efflux transporters protect brain cells from xenobiotics, therefore reducing brain exposure to intentionally administered drugs. In epilepsy, polymorphisms and overexpression of efflux transporters genes could be associated with pharmacoresistance. The ontogeny of these efflux transporters should also be addressed because their expression during development may be related to different brain exposure to antiepileptic drugs in the immature brain. We detected statistically significant higher expression of Abcb1b and Slc16a1 genes, and lower expression of Abcb1a and Abcg2 genes between the post-natal day 14 (P14) and the adult rat microvessels. P-gP efflux activity was also shown to be lower in P14 rats when compared with the adults. The P-gP proteins coded by rodent genes Abcb1a and Abcb1b are known to have different substrate affinities. The role of the Abcg2 gene is less clear in pharmacoresistance in epilepsy, nonetheless the coded protein Bcrp is frequently associated with drug resistance. Finally, we observed a higher expression of the Mct1 transporter gene in the P14 rat brain microvessels. Accordingly to our results, we suppose that age may be another factor influencing brain exposure to antiepileptics as a consequence of different expression patterns of efflux transporters between the adult and immature BBB.
authors.affiliation: Inserm U1129, Paris, France.|University Paris Descartes, Faculty of Medicine, Paris, France.|CEA, Direction des Sciences du Vivant, iBiTec-S, Service de Pharmacologie et d'Immunoanalyse, Gif-sur-Yvette, France.
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Soares
authors.affiliation: CEA, Direction des Sciences du Vivant, iBiTec-S, Service de Pharmacologie et d'Immunoanalyse, Gif-sur-Yvette, France.
authors.forename: Tuan M
authors.initials: TM
authors.lastname: Do
authors.affiliation: CEA, Direction des Sciences du Vivant, iBiTec-S, Service de Pharmacologie et d'Immunoanalyse, Gif-sur-Yvette, France.
authors.forename: Aloïse
authors.initials: A
authors.lastname: Mabondzo
authors.affiliation: Inserm U1129, Paris, France.|University Paris Descartes, Faculty of Medicine, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Pons
authors.affiliation: University Paris Descartes, Faculty of Medicine, Paris, France.|Inserm U1151, INEM, Paris, France.|APHP, Hôpital Universitaire Necker-Enfants Malades, Laboratoire d'immunologie biologique, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chhun
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D004351:Drug Resistance / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D055806:Microvessels / Q000378:metabolism*; D051381:Rats
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000927:Anticonvulsants; D027682:Cation Transport Proteins; D026901:Membrane Transport Proteins
keywords: ABC Transporters; SLC Transporters; blood-brain barrier; brain development; pharmacoresistance in Epilepsy