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.
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.