If oligos don’t die they can be saved

Cui QL, Khan D, Rone M, Rao V, Johnson RM, Lin YH, Bilodeau PA, Hall JA, Rodriguez M, Kennedy TE, Ludwin SK, Antel JP. Sublethal oligodendrocyte injury: A reversible condition in multiple sclerosis? Ann Neurol. 2017. doi: 10.1002/ana.24944. [Epub ahead of print]


Degeneration of oligodendroglial distal processes has been identified as an early event in MS lesion development. Our objective was to further define the development of the “dying-back” oligodendrocyte lesion in situ and to model the development and potential reversibility of such responses using dissociated cultures of adult human brain-derived oligodendrocytes. Methods In situ analyses were performed on glutaraldehyde-fixed thin sections of clinically acute and pathologically active cases of MS. In vitro studies were conducted using adult human brain-derived oligodendrocytes challenged by metabolic stress conditions (low nutrient/glucose).


In situ analyses indicated a spectrum of myelin changes in the presence of morphologically intact oligodendrocytes; these included degeneration of the inner cytoplasmic tongue with increasing sizes of intra-myelinic bleb formation (gaps between the lamellar/whirls of the myelin)  that could result in radial fractures of the myelin sheath. Macrophages with ingested myelin fragments were identified only once the fragmentation was established. In vitro studies indicated that oligodendrocyte process retraction that was linked to reduced glycolytic respiratory activity is reversible until a critical time point. Subsequent cell death was not linked to caspase-3 dependent programs. Gene expression studies conducted at the latest reversible time point revealed reduced expression of pathways associated with cell process outgrowth and myelination, as well as with metabolic activity.


Our findings reveal the potential to protect and possibly restore myelin elaborated by existent oligodendrocytes in early and evolving MS lesions, and suggest the necessity of ongoing studies on the mechanisms underlying subsequent adult human oligodendrocyte cell death.

DrLove and the gang from Holland have been looking at early oligodendrocyte damage for years and have termed these as pre-active lesions. There are too many of these pre-active lesions containing a stressed oligodendrocyte and activated microglia. They proposed many years ago that many of these lesions did not develop into full blown lesions. In this study they suggest that the problem is from within the oligodendrocyte and this causes damage to the myelin. There is process retraction was linked to metabolic effects. So if the the problem is within the oligodendrocyte then what are the genes affected.and focused on retraction of myelin processes, but this is going to a be a consequence I suspect. What else are in these cells, surely the thing that needs to be addressed is whether there is virus lurking in them. Is it HERV which will be in the genome of the oligodendrocytes but is there activity is it JC virus is it something else.

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  • But if it were a virus infecting oligodendrocytes, for example, could this be detected by the post mortem analysis of the oligos, or not?



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