Cited by 118Barrier Structure and Function StudiesMultiple Sclerosis Research StudiesCell Adhesion Molecules Research

Inflammation and Dephosphorylation of the Tight junction Protein Occludin in an Experimental Model of Multiple Sclerosis

Morgan, L., Shah, B., Rivers, L.E., Barden, L., Groom, A.J., Chung, R., Higazi, D., Desmond, H. +2 more·2007·Neuroscience

Abstract

Multiple sclerosis (MS) is a disease of the CNS in which inflammation, demyelination and neurodegeneration contribute to its initiation and progression. A frequently employed model of MS is experimental autoimmune encephalomyelitis (EAE). Here, to gain new insights into the disease process, an analysis of proteins in extracts of lumbar spinal cord from naïve and EAE rats was undertaken. The data mainly confirm that inflammation and blood-brain barrier (BBB) breakdown are the major hallmarks of disease in this model. Given their importance in the BBB, junctional proteins were further investigated. Occludin, a protein localizing to tight junctions in brain endothelial cells, showed strikingly increased migration in EAE when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This increased migration was mimicked by in vitro phosphatase treatment, implying its dephosphorylation in EAE. Occludin dephosphorylation coincided with the onset of inflammation, slightly preceding visible signs of disease, and was just prior to apparent changes in BBB permeability. These findings suggest occludin is a target for signaling processes in EAE, perhaps regulating the response of the BBB to the inflammatory environment as seen in MS.

Integrity signals

Registry

Crossref · 10.1016/j.neuroscience.2007.04.051

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56 of 56 references verified0 citation errors · 0 not checkable

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  • The severity of symptoms for MS and AD has been shown to be tightly coupled with BBB integrity, with onset and progression correlating strongly with BBB disruption.

    “the severity of symptoms for MS and AD have been shown to be tightly coupled with BBB integrity, with research indicating that onset and progression of symptoms correlates strongly with BBB disruption”

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Authors
Morgan, L., Shah, B., Rivers, L. E., Barden, L., Groom, A. J., Chung, R., Higazi, D., Desmond, H., Smith, T., & Staddon, J. M.
Affiliations
University College London (GB)
Venue
Neuroscience
Publisher
Elsevier BV
Published
2007-07
Volume
147
Issue
3
Pages
664-673
ISSN
0306-4522 (ISSN-L)
OpenAlex
W2095205887
Cited by
118
References
58
Citations by year
2025: 6 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 11 · 2012: 8
FWCI
5.10
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
multiple sclerosis, experimental autoimmune encephalomyelitis, occludin, tight junction proteins, protein dephosphorylation, blood-brain barrier disruption, myelitis, demyelination, phosphatase treatment, brain endothelial cells, blood-brain barrier permeability
MeSH terms
Animals, Disease Models, Animal, Encephalitis, Encephalomyelitis, Autoimmune, Experimental, Female, Membrane Proteins, Phosphoric Monoester Hydrolases, Phosphorylation, Rats, Inbred Lew, Mass Spectrometry, Spinal Cord, Electrophoresis, Gel, Two-Dimensional, Tight Junctions, Endothelial Cells, Immunoprecipitation, Rats, Occludin

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