Inflammation and dephosphorylation of the tight junction protein occludin in an experimental model of multiple sclerosis.

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.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Morgan L,Shah B,Rivers LE,Barden L,Groom AJ,Chung R,Higazi D,Desmond H,Smith T,Staddon JM

doi

10.1016/j.neuroscience.2007.04.051

subject

Has Abstract

pub_date

2007-07-13 00:00:00

pages

664-73

issue

3

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(07)00468-X

journal_volume

147

pub_type

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