title: Immunolocalization of tight junction proteins in the adult and developing human brain.
abstract: The formation of endothelial tight junctions (TJs) is crucial in blood-brain barrier (BBB) differentiation, and the expression and targeting of TJ-associated proteins mark the beginning of BBB functions. Using confocal microscopy, this study analyzed endothelial TJs in adult human cerebral cortex and the fetal telencephalon and leptomeninges in order to compare the localization of two TJ-associated transmembrane proteins, occludin and claudin-5. In the arterioles and microvessels of adult brain, occludin and claudin-5 form continuous bands of endothelial immunoreactivity. During fetal development, occludin and claudin-5 immunoreactivity is first detected as a diffuse labeling of endothelial cytoplasm. Later, at 14 weeks, the immunosignal for both proteins shifts from the cytoplasm to the interface of adjacent endothelial cells, forming a linear, widely discontinuous pattern of immunoreactivity that achieves an adult-like appearance within a few weeks. These results demonstrate that occludin and claudin-5 expression is an early event in human brain development, followed shortly by assembly of both proteins at the junctional areas. This incremental process suggests more rapid establishment of the human BBB, consistent with its specific function of creating a suitable environment for neuron differentiation and neurite outgrowth during neocortical histogenesis.
authors.affiliation: Department of Human Anatomy and Histology, University of Bari School of Medicine, Bari, Italy. virgintino@histology.uniba.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Virgintino
authors.forename: Mariella
authors.initials: M
authors.lastname: Errede
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.forename: Carmen
authors.initials: C
authors.lastname: Capobianco
authors.forename: Francesco
authors.initials: F
authors.lastname: Girolamo
authors.forename: Antonella
authors.initials: A
authors.lastname: Vimercati
authors.forename: Mirella
authors.initials: M
authors.lastname: Bertossi
authors.forename: Luisa
authors.initials: L
authors.lastname: Roncali
mesh_terms: D000368:Aged; D001812:Blood-Brain Barrier; D002540:Cerebral Cortex / Q000378:metabolism*; D062507:Claudin-5; D004730:Endothelium, Vascular / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008578:Meninges / Q000196:embryology* / Q000378:metabolism; D018613:Microscopy, Confocal; D008875:Middle Aged; D062793:Occludin; D013687:Telencephalon / Q000196:embryology* / Q000378:metabolism; D019108:Tight Junctions
chemical_list: C107466:CLDN5 protein, human; D062507:Claudin-5; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin