title: Increased expression of ER stress- and hypoxia-associated molecules in grey matter lesions in multiple sclerosis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: MS and Stroke Research Group, NCBES, National University of Ireland, Ireland.
authors.forename: J M
authors.initials: JM
authors.lastname: McMahon
authors.forename: S
authors.initials: S
authors.lastname: McQuaid
authors.forename: R
authors.initials: R
authors.lastname: Reynolds
authors.forename: U F
authors.initials: UF
authors.lastname: FitzGerald
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D015687:Cell Hypoxia; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology*