Research: Myelin breakdown attracts microglia

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Background: In multiple sclerosis (MS), gray matter pathology is characterized by less pronounced inflammation when compared with white matter lesions. Although regional differences in the cytoarchitecture may account for these differences, the amount of myelin debris in the cortex during a demyelinating event might also be contributory.
Objective: To analyze the association between myelin debris levels and inflammatory responses
Methods: Cortical areas with distinct and sparse myelination were analyzed for micro- and astrogliosis before and after cuprizone-induced demyelination in mice. In post-mortem tissue of MSers, leucocortical lesions (type III) were assessed for the type and level of inflammation in the cortical and white matter regions of the lesion. Furthermore, mice were injected intracerebrally with myelin-enriched debris, and the inflammatory response analyzed in white and grey matter areas.
Results: Our studies show that the magnitude of myelin loss positively correlates with microgliosis in the cuprizone model. In MS, the number of MHC class II expressing cells (microglia/macrophages) is higher in the white compared with the grey matter part of leucocortical lesions. Finally, direct application of myelin debris into the corpus callosum or cortex of mice induces profound and comparable inflammation in both regions.
Conclusion: Our data suggest that myelin debris is an important variable in the inflammatory response during demyelinating events.


 Macrophages (brown) in a lesion that crosses from the white matter (WM) 
into the cortex (CTX)/Grey Matter of the brain in MS

The leucocortical lesions of the grey matter cross the border with the white matter and are noted because on the grey matter side there a few white blood cells and on the white matter side there are lots of white blood cells. Are there different mechanisms for lesion formation in the white matter verses the grey matter. This is unlikely. On both sides the oligodendrocyte is the target and is associated with demylination (loss of myelin) from the nerve. This study suggests that the reason why white blood cells accumulate on the white matter side is simply because there is more myelin debris to eat and clear up.  The important question is what is damaging the oligodendrocyte?



CoI. Dr Love (Amor) is part of Team G

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MouseDoctor

5 comments

  • The oligodendrocytes are being damaged/killed by the administration of the toxin cuprizone, which kills oligodendrocytes.

  • Cuprizone is a toxin that is used to kill oligodendrocytes in experimental systems

    What damages the oligodendrocytes in MS, that is the thousand dollar question…Some argue stress then microglial come in others may say virus others may say antidodies to oligodendrocytes.

  • What you know what toxin kill the oligos then where is the problem? Couldn't you develop a drug to stop the toxin production etc.?

  • Anon, the toxin MD is talking about is the one they use in experiments to kill the oligos. It is not what kills them in MS- they don't know what kills them in MS

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