Research: Grey matter lesions


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 (Lack of oxygen)-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.

Inside of a cell

There are markers associated with the misfolding of protein strucutures in the protein factories (endoplasmic reticulum) of the cells in grey matter lesions in MSers. The production of CHOP favours the production of cell death, because it causes down regulation of mitochondrial protein Bcl-2, that controls and protects cells from death. This therefore favouring a pro-cell death drive at the mitochondria (the energy powerhouse of the cell) by proteins that cause mitochondrial and cell damage. These authors suggest that there may be damage caused by hypoxia. This is lack of oxygen, which occurrs in stroke where it is associated with blocked vessels. However, these molecules are associated with patholgy. This study tells us that there are damaging processes occuring in MS lesions.

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  • I have no idea how scientists have managed to discover so much about the inner-workings of a human cell.

    I take it what you're talking about is oxadative-stress?

  • Hi Maria,
    This evidence is at the level of the microvasculature (very small blood vessels)in the brain, rather than the macro level posited by the theory that we daren't speak of.

  • "I take it what you're talking about is oxadative-stress?"

    No not really oxidative stress, which is about free radicals and hydrogen peroxide and superoxide etc, but this is more related to issues about folding proteins into their correct shape and heat shock proteins and chaperone function. All big words but it means the cells are not happy chappies

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