Fetal blood-brain barrier P-glycoprotein contributes to brain protection during human development.
During brain development and blood-brain barrier (BBB) differentiation the expression of P-glycoprotein (P-gp) may complement the protective function of the placental barrier against xenobiotic substances. To establish an immunohistochemical procedure for P-gp detection, different anti-P-gp monoclonal antibodies were first tested on a fibrosarcoma cell line and colonic carcinoma tissue. The protocol was then tested on adult human brains as a BBB-P-gp tissue-specific control and for double labeling with anti-P-gp and the astroglia marker glial fibrillary acidic protein (GFAP). The protocol was then used to analyze the expression and localization of P-gp in human fetuses during cerebral cortex formation. At the earliest examined stage, 12 weeks of gestation (wg), P-gp was detectable as diffuse cytoplasmic labeling of the endothelial cells lining the primary cortex microvessels. At 18 wg, a punctate P-gp staining pattern was detected on cortex and subcortical vessels and on their side branches. At 22 wg, P-gp staining was linear and concentrated on endothelial cell membranes. In all examined ages, GFAP-positive radial glial cells and astrocytes did not stain for P-gp, even at their perivascular processes, whereas faint P-gp labeling was seen on vimentin-reactive radial glia at the earliest examined fetal age. At midgestation, P-gp colocalized with caveolin-pY14 on the abluminal endothelial cell membrane. These results demonstrate that P-gp is expressed early during human cerebral cortical microvessel development, and suggest that at midgestation there may be efflux activity that is regulated by interactions with the caveolar endothelial cell compartment.
Virgintino
Daniela
D
Department of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy. virgintino@histology.uniba.it
Errede
Mariella
M
Girolamo
Francesco
F
Capobianco
Carmen
C
Robertson
David
D
Vimercati
Antonella
A
Serio
Gabriella
G
Di Benedetto
Adriana
A
Yonekawa
Yasuhiro
Y
Frei
Karl
K
Roncali
Luisa
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000328:Adult; D000367:Age Factors; D001812:Blood-Brain Barrier / Q000196:embryology* / Q000378:metabolism*; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D022461:Caveolins / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D005260:Female; D005333:Fetus; D005354:Fibrosarcoma / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006803:Human Development / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014746:Vimentin / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D022461:Caveolins; D005904:Glial Fibrillary Acidic Protein; D014746:Vimentin