title: Fetal blood-brain barrier P-glycoprotein contributes to brain protection during human development.
abstract: 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.
authors: Department of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy. virgintino@histology.uniba.it
authors: Daniela
authors: D
authors: Virgintino
authors: Mariella
authors: M
authors: Errede
authors: Francesco
authors: F
authors: Girolamo
authors: Carmen
authors: C
authors: Capobianco
authors: David
authors: D
authors: Robertson
authors: Antonella
authors: A
authors: Vimercati
authors: Gabriella
authors: G
authors: Serio
authors: Adriana
authors: A
authors: Di Benedetto
authors: Yasuhiro
authors: Y
authors: Yonekawa
authors: Karl
authors: K
authors: Frei
authors: Luisa
authors: L
authors: Roncali
mesh_terms: 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
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D022461:Caveolins; D005904:Glial Fibrillary Acidic Protein; D014746:Vimentin