Long-term regulation of microglia: Role of epigenetic mechanisms, inflammatory events and diet

The central research question in this doctoral dissertation is what the effects are of acute, but especially the long-term effects of microglia activation on microglia themselves and its effect on the brain. Microglia are immune cells in the brain that are capable of recognizing and clearing damaged or dead cells or harmful microorganisms in the centrals nervous system. With these activities, immune functions of the cells are activated and inflammation occurs. Also, microglia are involved in mechanisms that support neurons and produce factors that are favorable to neuronal function. This begins well before birth, during embryonic development, which means that early changes in the functioning of these cell can lead to serious implications later in life. An important note in the central question of this thesis, which are the long-term effects of microglia activation, is that microglia are cells that normally are not replaced by cells from other locations in the body. They can replace themselves through cell division, but under normal circumstances this does not happen on a large scale. Because of this, some microglia can be decades old. Both short-term and chronic neuroinflammation can leave behind sort of a fingerprint in microglia, which can change the properties, the response and the normal functioning of these cells in future disease or during normal aging.In this thesis we investigated (epi) genetic regulation of neuroinflammation, as well as the effect of inflammation, diet and maternal inflammation on microglia functioning.