title: Differences in the molecular structure of the blood-brain barrier in the cerebral cortex and white matter: an in silico, in vitro, and ex vivo study.
abstract: The blood-brain barrier (BBB) is the main interface controlling molecular and cellular traffic between the central nervous system (CNS) and the periphery. It consists of cerebral endothelial cells (CECs) interconnected by continuous tight junctions, and closely associated pericytes and astrocytes. Different parts of the CNS have diverse functions and structures and may be subject of different pathologies, in which the BBB is actively involved. It is largely unknown, however, what are the cellular and molecular differences of the BBB in different regions of the brain. Using in silico, in vitro, and ex vivo techniques we compared the expression of BBB-associated genes and proteins (i.e., markers of CECs, brain pericytes, and astrocytes) in the cortical grey matter and white matter. In silico human database analysis (obtained from recalculated data of the Allen Brain Atlas), qPCR, Western blot, and immunofluorescence studies on porcine and mouse brain tissue indicated an increased expression of glial fibrillary acidic protein in astrocytes in the white matter compared with the grey matter. We have also found increased expression of genes of the junctional complex of CECs (occludin, claudin-5, and α-catenin) in the white matter compared with the cerebral cortex. Accordingly, occludin, claudin-5, and α-catenin proteins showed increased expression in CECs of the white matter compared with endothelial cells of the cortical grey matter. In parallel, barrier properties of white matter CECs were superior as well. These differences might be important in the pathogenesis of diseases differently affecting distinct regions of the brain.
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary;
authors.forename: Ádám
authors.initials: Á
authors.lastname: Nyúl-Tóth
authors.affiliation: Institute of Life Sciences, Vasile Goldis Western University of Arad, Arad, Romania; and.
authors.forename: Maria
authors.initials: M
authors.lastname: Suciu
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary;
authors.forename: Judit
authors.initials: J
authors.lastname: Molnár
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary;
authors.forename: Csilla
authors.initials: C
authors.lastname: Fazakas
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary;
authors.forename: János
authors.initials: J
authors.lastname: Haskó
authors.affiliation: Institute of Life Sciences, Vasile Goldis Western University of Arad, Arad, Romania; and.
authors.forename: Hildegard
authors.initials: H
authors.lastname: Herman
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary;
authors.forename: Attila E
authors.initials: AE
authors.lastname: Farkas
authors.affiliation: Institute of Surgical Research, University of Szeged, Szeged, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Kaszaki
authors.affiliation: Institute of Life Sciences, Vasile Goldis Western University of Arad, Arad, Romania; and.
authors.forename: Anca
authors.initials: A
authors.lastname: Hermenean
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary;
authors.forename: Imola
authors.initials: I
authors.lastname: Wilhelm
authors.affiliation: Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary; Institute of Life Sciences, Vasile Goldis Western University of Arad, Arad, Romania; and krizbai.istvan@brc.mta.hu.
authors.forename: István A
authors.initials: IA
authors.lastname: Krizbai
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003198:Computer Simulation; D005260:Female; D066128:Gray Matter / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D020286:Pericytes / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism*; D013552:Swine; D062725:Tight Junction Proteins / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism; D066127:White Matter / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D036341:Intercellular Signaling Peptides and Proteins; D017978:Receptors, Growth Factor; D062725:Tight Junction Proteins
keywords: Allen Brain Atlas; GFAP; astrocyte; blood-brain barrier; cerebral endothelial cell; neurovascular unit; pericyte; tight junction