Multiple Sclerosis (MS) is an incurable neurological disorder that is characterized by the loss of specialized functional cells in our brain. Oligodendrocytes are one of these specialized cell types that play an important role in MS. They produce a fatty substance called myelin, which is produced in large sheaths that are tightly wrapped around our nerve cells. Myelin is essential for providing nutrients to them, but also to speed up our brain activity. In MS, myelin and oligodendrocytes are lost for unknown reasons, resulting in the distinct lesions that are visible in MRI scans. Human brains are quite flexible, they can initially cope with this loss and eventually repair the damage – a process that we call remyelination – but in the long run, the remyelination capacity of oligodendrocytes decreases and the lesions remain. As the nerve cells are losing both their protection and their fuel, they degenerate in late stages of MS, leading to the various devastating symptoms of people living with the disease.
Although we know what happens during the disease, the reasons for this are less well understood and a lot of current research – including ours – is addressing this question. We are using a novel technology called single-nuclei RNA-sequencing that allows us to analyse thousands of individual brain cells at a much deeper resolution than ever before. With this, we compared oligodendrocytes of post-mortem brains of people that were living with MS and non-neurological controls to better understand the oligodendrocyte biology of the human brain and to detect the pathological changes of the disease. In our recent publication (Jaekel et al. 2019), we found that our brain contains distinct subtypes of oligodendrocytes that can be distinguished by the expression of different markers. We think that these heterogeneous oligodendrocytes do have different functions. Our current and future research is focusing on this. In MS, the composition of these subtypes is shifted, with some subtypes being over- and some underrepresented. We don’t know yet whether this skew in oligodendrocyte heterogeneity is the result of some oligodendrocytes being more prone to death or some oligodendrocytes being predominantly replaced.
Available medication is targeting the immunological component in early stages of the disease, which proves to be efficient for a limited time. Unfortunately, there is no available therapy tackling brain repair and nerve cell degeneration at the later stages of the disease. Current research strategies for new therapeutic approaches are therefore aiming at improving the new generation of oligodendrocytes and thus active remyelination. By gaining a better knowledge about oligodendrocytes in our brain, our work is a very important step towards understanding the cellular changes that are happening in this disease and thus paves the way for new strategies to treating MS.
By Sarah Jaekel
Sarah Jaekel (nee Schneider) is a postdoctoral research fellow at the Centre for Regenerative Medicine (University of Edinburgh, Scotland). Her main research interest focuses on human oligodendrocyte heterogeneity in healthy brains as well as in neurodegenerative diseases such as Multiple Sclerosis and Alzheimers.
After finishing her Master’s degree in Molecular Biotechnology in 2011, Sarah became interested in neuroscience – particularly in oligodendroglia. During her PhD, which she obtained from the Graduate School of Systemic Neuroscience at the Ludwig-Maximilians-University in Munich (Germany) in 2016, she elaborated the role of proliferating oligodendrocyte progenitor cells in health and disease in rodents. In order to extend her research to humans, Sarah moved to Edinburgh to start her current position. With her work on human oligodendrocytes, she was awarded the European Marie-Skłodowska Curie fellowship in 2018. Sarah is