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Differences in expression of junctional adhesion molecule-A and β-catenin in multiple sclerosis brain tissue: increasing evidence for the role of tight junction pathology

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Abstract

Previously we have employed antibodies to the tight junction (TJ)-associated proteins ZO-1 and occludin to describe endothelial tight junction abnormalities, in lesional and normal appearing white matter, in primary and secondary progressive multiple sclerosis (MS). This work is extended here by use of antibodies to the independent TJ-specific proteins and junctional adhesion molecule A & B (JAM-A, JAM-B). We have also assessed the expression in MS of β-catenin, a protein specific to the TJ-associated adherens junction. Immunocytochemistry and semiquantitative confocal microscopy for JAM-A and β-catenin was performed on snap-frozen sections from MS cases (n = 11) and controls (n = 6). Data on 1,443 blood vessels was acquired from active lesions (n = 13), inactive lesions (n = 13), NAWM (n = 20) and control white matter (n = 13). In MS abnormal JAM-A expression was found in active (46%) and inactive lesions (21%), comparable to previous data using ZO-1. However, a lower level of TJ abnormality was found in MS NAWM using JAM-A (3%) compared to ZO-1 (13%). JAM-B was strongly expressed on a small number of large blood vessels in control and MS tissues but at too low a level for quantitative analysis. By comparison with the high levels of abnormality observed with the TJ proteins, the adherens junction protein β-catenin was normally expressed in all MS and control tissue categories. These results confirm, by use of the independent marker JAM-A, that TJ abnormalities are most frequent in active white matter lesions. Altered expression of JAM-A, in addition to affecting junctional tightness may also both reflect and affect leukocyte trafficking, with implications for immune status within the diseased CNS. Conversely, the adherens junction component of the TJ, as indicated by β-catenin expression is normally expressed in all MS and control tissue categories.

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Acknowledgments

Suzie Leech was the recipient of a 1-year post-doctoral fellowship from MS Ireland. The Leica SP2 confocal microscope was purchased with a Wellcome Trust Equipment grant (069411/Z/02/Z). Tissue samples were supplied by the UK Multiple Sclerosis Tissue Bank, funded by the Multiple Sclerosis Society of Great Britain and Northern Ireland.

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Authors and Affiliations

  1. Conway Institute, School of Biomolecular and Biomedical Research, UCD, Dublin, Ireland

    Maureen Padden & Brenda Brankin

  2. Neuropathology Laboratory, Institute of Pathology, Royal Group of Hospitals Trust, Grosvenor Road, Belfast, BT12 6BL, Northern Ireland, UK

    Beverly Craig & Stephen McQuaid

  3. Multiple Sclerosis Molecular Pathology Research Group, School of Medicine, Queen’s University Belfast, Institute of Pathology, Belfast, UK

    Susie Leech & John Kirk

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  1. Maureen Padden
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  2. Susie Leech
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Correspondence to Stephen McQuaid.

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Padden, M., Leech, S., Craig, B. et al. Differences in expression of junctional adhesion molecule-A and β-catenin in multiple sclerosis brain tissue: increasing evidence for the role of tight junction pathology. Acta Neuropathol 113, 177–186 (2007). https://doi.org/10.1007/s00401-006-0145-x

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