Erik Nutma

24 Chapter 1 Over the last decade knowledge of the role of astrocytes in CNS neuroinflammatory diseases has changed dramatically. Rather than playing a merely passive role in response to damage it is clear that astrocytes are increasingly implicated in exerting immunological relevant functions within the CNS. Whilst most astrocyte research focuses on modulating neuronal function and synaptic transmission little is known about the cross-talk between astrocytes and oligodendrocytes, the myelinating cells of the CNS. We thus reviewed evidence for the immunological roles astrocytes and oligodendrocytes play and how the two cell types interact (Chapter 7). As primary innate immune cells in the CNS, microglia play critical roles in shaping the brain during development, responding to pathogens, and clearing tissue debris or protein aggregations during ageing, neuroinflammation and neurodegeneration. The last decade has given us many new insights in the heterogeneity of microglia states. However, many of the single cell/nucleus RNA-seq studies have focused on microglia in the grey matter or of the whole brain while ignoring the heterogeneity of microglia in the white matter. Therefore, we provide an update on the current knowledge of microglia heterogeneity in the white matter and how microglia are important for development of the white matter as well as how ageing affects white matter homeostasis (Chapter 8). To conclude this thesis, the results of the previous chapters are summarised. The data in this thesis is discussed and put into context, which enables us to give an overview on the current knowledge of innate immune cells in the CNS, and how to monitor these cells in vivo during neuroinflammation (Chapter 9).

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