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

• Published in: Multiple sclerosis Vol. 18; no. 10; pp. 1437 - 1447
• Main Authors: McMahon, JM, McQuaid, S, Reynolds, R, FitzGerald, UF
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.10.2012; Sage Publications; Sage Publications Ltd
• 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; ER stress; hypoxia; grey matter lesions; human tissue; multiple sclerosis; Human; Oxygen; Nervous system diseases; Multiple sclerosis; Grey matter; Stress; Inflammatory disease; Central nervous system disease; Hypoxia; Degenerative disease
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458512438455

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.