The brain disease multiple sclerosis (MS) is characterised by inflammation in the brain and spinal cord. In addition to inflammation, myelin, the protective layer surrounding nerve fibers, also disappears. Several years ago, the presence of myelin swellings in the brain tissue of people with MS, even though no inflammation was visible, was first described. Because of this, myelin swellings are sometimes considered precursors to inflammation.
Dynamic damage
The research team used advanced microscopy techniques developed by VU physicist Marloes Groot and various models—from zebrafish and mice to human brain tissue—to investigate the formation of this damage. PhD candidate Niels Meijns: "This allowed us to determine that myelin swellings have a conserved, dynamic nature: they can not only grow, but also shrink and even recover completely. The activity of the underlying nerve fiber appears to play a key role in this; increased activity leads to larger and more swellings, while decreased activity actually facilitates recovery." The results have been published in Science.
Advanced models
The strength of this study lies in the combination of different models and techniques, giving the researchers the opportunity to study the processes in both animal models and human tissue in an identical way. In traditional brain research, the tissue structure is usually frozen with chemicals, making it impossible to determine the dynamic nature of the myelin swelling. In the collaboration between the laser lab and Amsterdam UMC, third-harmonic generation (THG) microscopy was used, while two-photon microscopy was performed at the Netherlands Institute for Neuroscience. Using these microscopy techniques, myelin changes in tissue could be studied in three dimensions and over time. These techniques offer valuable starting points for further research into the development and repair of lesions in MS.
Beginning of myelin swelling
The next step is to explore why the activity of the nerve fibres can change the size and amount of myelin swellings. The researchers also want to study the role of brain cells in the appearance and disappearance of myelin swellings. Using the published model systems, the team of Maarten Kole (NIN) and Antonio Luchicchi (MS Center Amsterdam, Amsterdam UMC), together with the team of David Lyons (Edinburgh), will seek to address these questions. Addressing this early damage, before myelin is lost, could offer new treatment options in the future for preventing tissue damage in MS and helping to keep myelin healthy for longer.
This research is made possible by MS Centrum Amsterdam, Nationaal MS Fonds, Progressive MS Alliance, The Friends Foundation of the Netherlands Institute for Neuroscience and NWO