Increased expression of ER stress- and hypoxia-associated molecules in grey matter lesions in multiple sclerosis

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 objectiv...

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Bibliographic Details
Published in:Multiple sclerosis 2012-10, Vol.18 (10), p.1437-1447
Main Authors: McMahon, JM, McQuaid, S, Reynolds, R, FitzGerald, UF
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biological and medical sciences
Brain - metabolism
Brain - pathology
Cell Hypoxia
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Endoplasmic Reticulum Stress - physiology
Female
Fluorescent Antibody Technique
Humans
Immunohistochemistry
Male
Medical sciences
Middle Aged
Multiple Sclerosis - metabolism
Multiple Sclerosis - pathology
Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis
Neurology
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Summary: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.
ISSN:1352-4585
1477-0970
DOI:10.1177/1352458512438455