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McMahon, JM,McQuaid, S,Reynolds, R,FitzGerald, UF
2012
October
Multiple Sclerosis Journal
Increased expression of ER stress- and hypoxia-associated molecules in grey matter lesions in multiple sclerosis
Published
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Optional Fields
multiple sclerosis grey matter lesions ER stress human tissue hypoxia ENDOPLASMIC-RETICULUM STRESS MITOCHONDRIAL DYSFUNCTION WHITE-MATTER INJURY PROTEIN CHOP DEATH CELLS DEMYELINATION PATHOLOGY
18
1437
1447
Background: The endoplasmic reticulum (ER) stress pathway may play a role in the pathogenesis multiple sclerosis (MS), and while ER stress-associated molecules have been demonstrated in white matter (WM) lesions, these have not been analysed in grey matter (GM) demyelination.Objective: The objective was to characterise the type and frequency of GM lesions and establish expression profiles of ER stress-and hypoxia-associated markers.Methods: Sections from 16 MS cases and 12 non-MS controls were stained for ER stress molecules (BiP and CHOP) and hypoxia-associated D110 antigen.Results: Of the GM lesions analysed, 24% were type 1 (continuous between GM and WM), 22% were type 2 (entirely within GM) and the majority (54%) were type 3 (extending from pia mater). Comparison of GM lesions, MS normal-appearing grey matter (NAGM) and non-MS control tissue showed that NAGM, type 1 and type 3 lesions all had significantly increased levels of CHOP compared to controls. According to morphological and dual-labelling criteria, the majority of CHOP-positive cells were microglia. Approximately 50% of GM lesions contained D110-positive cells.Conclusion: These data suggest that ER stress plays an important role in GM lesion development and may be critical in activation of microglia in pre-lesional NAGM. The high number of lesions containing D110-positive cells suggests a role for hypoxic-like insult in GM lesion development.
DOI 10.1177/1352458512438455
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