October 22, 2009

You can think of the human body as a machine, and you can also think of its individual components (cells, structures, organs) as components of this machine. The structural and mechanical properties of the body's components affect how well the machine operates -- that is, they play a role in sickness and health. These properties of the body don't receive much attention in MS, compared with other aspects such as immune activation and signaling. However, as shown by two recent papers dealing with mechanical properties and functions, perhaps they play key roles and could potentially provide new areas for therapies.

The first paper presents a theory that remyelination (or lack thereof) in MS is influenced by two types of physical forces -- forces within the oligodendrocyte precursor cells that move into a demyelinated lesion, and forces outside those cells. Studies suggest that a balance between these forces is needed for these precursor cells to become oligodendrocytes and start extending myelin sheets to wrap around neighboring axons. If that balance is off -- for example, if astrocyte scarring in a lesion results in a more physically rigid environment -- then the precursors may be inhibited from initiating the remyelination process. Factors within the precursor cell that control its own rigidity and ability to contract can also influence the activities of the cell including myelination. Further study of these factors could therefore result in ideas for therapies to enhance remyelination in people with MS or similar diseases.

The second paper presents results from a study of how interferon-beta (IFN-b) affects the mechanical properties of astrocytes. Among other functions, astrocytes provide structural support in the brain and as mentioned above, can form rigid scar tissue in MS lesions. In a series of experiments, astrocytes in a cell culture were exposed to IFN-b and then analyzed by special microscopes to see whether their shape and rigidity had changed. After IFN-b exposure, the cells retained the same basic shape -- cell bodies with a few armlike extensions -- although the post-IFN-b cells had a smoother surface texture. However, rigidity of the cells was affected (decreased) by IFN-b exposure. Further analysis revealed changes in the generation of certain proteins by the astrocytes that would appear to be responsible for this decreased stiffness.

Although it's too soon to draw a solid line between these two studies, it may be that one of the benefits of IFN-b in MS is to change the properties of astrocytes so that they are less rigid and more permissive of remyelination activities.

Both of these papers are available to read online (the first one permanently, the second one for at least another week or two), so if you have an engineering background like me, you might find them particularly interesting. The second paper also has some nice images of living astrocytes in case you're curious about what they look like!