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Neuropediatrics 2008; 39(4): 211-218
DOI: 10.1055/s-0028-1103272
Original Article

© Georg Thieme Verlag KG Stuttgart · New York

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

M. Daood 1 , C. Tsai 1 , M. Ahdab-Barmada 2 , J. F. Watchko 1
  • 1Division of Newborn Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA
  • 2The WHY-NMD Institute, Pittsburgh, Pennsylvania, USA
Further Information

Publication History

received 23.01.2008 revised 24.06.2008

accepted 21.10.2008

Publication Date:
22 January 2009 (online)

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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 220/7–420/7 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 220/7 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.

Key words

BCRP - P-glycoprotein - MRP1 - blood-brain barrier - human neonates

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Correspondence

J. F. WatchkoMD 

Division of Newborn Medicine

Department of Pediatrics

Magee-Womens Hospital

300 Halket Street

Pittsburgh

15213 Pennsylvania

USA

Phone: +1/412/641 18 34

Fax: +1/412/641 53 13

Email: jwatchko@mail.magee.edu