Study reveals dynamic nature of myelin swellings

An international research team of Amsterdam UMC, VU LaserLab, the Netherlands Institute for Neuroscience and the University of Edinburgh have gained new insights into the dynamics of myelin swellings in the brain. Myelin swellings are considered as the precursor of lesions in the brain of people with multiple sclerosis (MS). The results have been recently published in the leading magazine Science.

MS is characterised by lesions in the brain and the spinal cord. Aside from these inflammations, damage can also be visible in the myelin; the protective layer surrounding nerve fibers. Myelin swellings are seen as a precursor for damaged myelin.

Dynamic damage

The research team used advanced microscopy techniques and different models – from zebrafish and mouse models to human brain tissue – to research the formation of this damage. This led to the discovery that myelin swellings have a dynamic character: they can not only grow, but also shrink and even recover completely. It also turns out that the activity of the underlying nerve fibre plays an important role; more activity of the nerve fibre leads to more and bigger swellings, while less activity allows for possible recovery.

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.

Start of myelin swellings

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, even before myelin is lost, could offer in the future new treatment possibilities for MS and help keep myelin healthy for longer.