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

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.