P-glycoprotein expression in mouse brain increases with maturation.
The mdr1a isoform of P-glycoprotein (Pgp) is an integral plasma membrane efflux pump expressed in adult brain capillary endothelial cells and astrocytes of the blood-brain barrier. We determined the developmental pattern of Pgp expression in brain tissue at embryonic day 16 (E16), day of life 0 (D0), day of life 7 (D7), day of life 21 (D21), and adults (Ad). The relative expression of Pgp mRNA and protein was indexed as a percent (mean +/- SEM) of D0 levels. Pgp mRNA levels increased significantly (p < 0.01) with maturation (E16: 75 +/- 8%; D21: 303 +/- 37%, and Ad: 1,160 +/- 120%). Similarly, Pgp protein expression was observed at E16 and increased significantly (p < 0.01) during development (E16: 52 +/- 8%; D7: 187 +/- 23%; D21: 440 +/- 48%, and Ad: 441 +/- 56%). This developmental pattern of enhanced blood-brain barrier Pgp expression with maturation was confirmed by immunohistochemistry. We conclude that (i) Pgp expression in mouse brain is limited during late embryogenesis and the newborn period; (ii) Pgp expression increases markedly with postnatal maturation, and (iii) by D21 brain Pgp protein expression approximates adult levels.
Tsai
Catherine E
CE
Department of Pediatrics, Magee-Womens Hospital/Research Institute, University of Pittsburgh School of Medicine, 300 Halket Street, Pittsburgh, PA 15213, USA.
Daood
Monica J
MJ
Lane
Robert H
RH
Hansen
Thor W R
TW
Gruetzmacher
Elisa M
EM
Watchko
Jon F
JF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000235:genetics*; D000375:Aging; D000818:Animals; D001812:Blood-Brain Barrier; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000196:embryology / Q000254:growth & development*; D001923:Brain Chemistry; D015870:Gene Expression; D007150:Immunohistochemistry; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger