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ABC transporter (P-gp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing human CNS

M Daood1, C Tsai, M Ahdab-Barmada

  • 1Division of Newborn Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213, USA.

Neuropediatrics
|January 24, 2009
PubMed

Insights

This study investigated the expression of key drug efflux pumps, P-glycoprotein (P-gp/ABCB1), MRP1/ABCC1, and BCRP/ABCG2, in the developing human brain. These proteins show specific developmental patterns and cellular localization, influencing drug and toxin entry into the neonatal central nervous system.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Developmental Biology

Background:

  • Plasma membrane efflux pumps like P-glycoprotein (P-gp/ABCB1), multidrug resistance associated protein 1 (MRP1/ABCC1), and breast cancer resistance protein (BCRP/ABCG2) are crucial for limiting the brain's uptake of xenobiotics and endobiotics.
  • Limited information exists regarding the expression patterns of these efflux pumps during human neonatal and developmental stages within the central nervous system (CNS).

Purpose of the Study:

  • To determine the ontogeny and cellular localization of P-gp/ABCB1, MRP1/ABCC1, and BCRP/ABCG2 in the developing human CNS.
  • To understand how the expression of these efflux pumps changes from early gestation to adulthood.

Main Methods:

  • Immunostaining of post-mortem human CNS tissue from infants (22 weeks gestation to term) and adults.
  • Analysis of P-gp/ABCB1, MRP1/ABCC1, and BCRP/ABCG2 expression in various CNS regions and cell types.

Main Results:

  • P-gp/ABCB1 was detected in microvessel endothelial cells early (22 weeks), increasing with maturation, and later in pyramidal neurons.
  • MRP1/ABCC1 was prominent in the choroid plexus and ventricular ependyma early, and later in pyramidal neurons.
  • BCRP/ABCG2 expression was primarily observed in microvessel endothelial cells.
  • Expression in adult brains generally matched term newborns but showed higher intensity.

Conclusions:

  • P-gp/ABCB1, MRP1/ABCC1, and BCRP/ABCG2 exhibit developmental and cell-specific expression in the human CNS.
  • The distinct localization of these pumps at the blood-brain barrier (P-gp/ABCB1, BCRP/ABCG2) and blood-CSF barrier (MRP1/ABCC1) likely modulates drug and toxin penetration in neonates.

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