PhD defence W.M. (Woutje) Berdowski

Brief summary of the doctoral thesis:

White matter and glial cellular abnormalities have been implicated in various common neurodegenerative diseases, including Alzheimer’s disease. Therefore, it is important to better understand how white matter can be an Achilles heel for brain health, by gaining insight into the development and maintenance of white matter and how glia play a role in these processes. This will aid in better understanding the pathogenesis of different brain diseases where white matter is implicated, and provides clues for the development of novel therapeutic strategies in the future.

To better understand the development of white matter and the various roles of glia in this process, we generated zebrafish models for three different genetic white matter disorders, named ‘leukodystrophies’, and studied early cellular processes in their larvae in the context of leukodystrophy. As genetic techniques develop rapidly, we are now able to generate mutations in the zebrafish genome that in patients cause the disease. Therefore, we can study brain development of “patient-specific” mutants, which increases the relevance of our findings in the fish for patients. With this work, we contributed to knowledge about the underlying mechanisms of these three leukodystrophies, but also to a wider understanding of the role of glial cellular mechanisms in the development and maintenance of healthy white matter. This can aid in improving our understanding of white matter biology in healthy and diseased brain, which in term can be used in the development of novel treatment strategies in brain diseases where white matter in implicated.