Areas of inflammation in the brain a grey area

• Brain tissue can be split into two kinds, grey matter (mainly nerve cell bodies and branching connections) and white matter (mainly long tracts of nerve fibres coated with myelin).
• Traditionally a lot of focus in MS has been on the white matter but new research highlights the role of the grey matter damage within the brain in MS.
• This research possibly uncovers a new autoimmune disease process in MS targeting cells in the grey matter.

Brain tissue can be roughly divided in two types, grey matter and white matter. Most of the grey matter can be found on the outer portions of the brain and the white matter on the inner portions. Not surprisingly these two areas of the brain have been named after their physical colour, the grey matter, which has a pinkish-grey colour in the living brain and the white area which has a whitish appearance.

Typically MS has been thought to be a disease of the white matter, as this is the area where there are tracts of myelinated nerve fibres, and in MS the immune system is known to attack and damage the myelin coating on myelinated nerve fibres. Further emphasis has been placed on the white matter as areas of damage in these areas are readily detected in MRI scans, and experimental models of MS are made by generating an immune response against myelin. However, more recently it has become clear that MS can involve both the white and grey areas, and there might be two different mechanisms. One where the immune system attacks the myelin sheath in the white matter creating the classic MS lesions as seen in an MRI, and the second causing damage to nerve cells (neurons) leading to neurodegeneration in the grey matter.

Evidence suggests that this damage to the grey matter may be primarily responsible for loss of brain volume seen in people with MS (brain atrophy) and the accumulation in MS symptoms. There is also evidence that this grey area damage may be more prominent in people with progressive MS.

Now, research published in the prestigious scientific journal Nature by a group of German scientists suggests that the immune system is not just attacking the myelin on nerve fibres in the white matter, but is also targeting a protein found in the grey matter called beta-synuclein, thus providing a mechanism by which the neurodegeneration in the grey matter is occurring.

The scientists showed that people with MS not only have immune cells floating around their blood which could target their own myelin , but also immune cells which could target beta-synuclein. They also showed that people with relapsing remitting MS might have slightly more cells targeting myelin whereas those with progressive MS have relatively higher levels of cells targeting beta-synuclein.

They went on to show in experimental models of MS, that when immune cells targeting beta-synuclein were added, they were able to get through the blood brain barrier and cause a flare of symptoms. However, after multiple flare ups they found that the immune cells in the brain became persistently active, potentially leading to a continual attack on the cells in this part of the brain which might lead to a more progressive course of the disease.

Overall this research shows that there is additional disease mechanisms in MS which may be more active in progressive MS. This new information may open not only new avenues of research for the development of individual prognostic tests to predict the outcomes of an individual’s diagnosis but also possibly new therapeutic measures for people with MS especially those with progressive MS.

With thanks to MS Research Australia – the lead provider of research summaries on our website.