Increased Expression of ER Stress- And Hypoxia-Associated Molecules in Grey Matter Lesions in Multiple Sclerosis

Mult Scler. 2012 Oct;18(10):1437-47. doi: 10.1177/1352458512438455. Epub 2012 Feb 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain / metabolism*
  • Brain / pathology*
  • Cell Hypoxia
  • Endoplasmic Reticulum Stress / physiology*
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / pathology*