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Immunolocalization of tight junction proteins in the adult and developing human brain

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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.

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Acknowledgements

The authors are grateful to Prof. S. Nag for critical reading of the manuscript. The authors also thank Ms M.V.C. Pragnell, BA, for linguistic help and Ms M. Ambrosi for excellent technical assistance. This work was supported by grants from the Ministero dell’Istruzione, dell’Università e della Ricerca (M.I.U.R.) (to L.R.).

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Authors and Affiliations

  1. Department of Human Anatomy and Histology, University of Bari School of Medicine, Bari, Italy

    Daniela Virgintino, Mariella Errede, Francesco Girolamo & Luisa Roncali

  2. Breakthrough Centre, Institute of Cancer Research, London, UK

    David Robertson

  3. Department of Emergency and Organ Transplantation, University of Bari School of Medicine, Bari, Italy

    Carmen Capobianco

  4. Institute of Obstetric and Gynecology II, University of Bari School of Medicine, Bari, Italy

    Antonella Vimercati

  5. Department of Biomedical Sciences, University of Foggia School of Medicine, Foggia, Italy

    Mirella Bertossi

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  1. Daniela Virgintino
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  2. Mariella Errede
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  4. Carmen Capobianco
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  5. Francesco Girolamo
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Correspondence to Daniela Virgintino.

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Daniela Virgintino and Mariella Errede contributed equally to this work

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Virgintino, D., Errede, M., Robertson, D. et al. Immunolocalization of tight junction proteins in the adult and developing human brain. Histochem Cell Biol 122, 51–59 (2004). https://doi.org/10.1007/s00418-004-0665-1

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