Central role in cleaning and maintaining the brain
Microglia cells are at the forefront of the brain's immune defence. For example, they eliminate invading bacteria by engulfing and processing them in their 'stomachs' called phagosomes. These phagosomes act as a kind of 'waste recycling', using digestive enzymes to break down the enveloped invaders. Dead endogenous cells or cell components are also removed and recycled daily by phagocytes in the healthy brain. Scientists agree that the removal of cellular waste plays an important role in brain development, both in the healthy brain and in diseases such as Alzheimer's and brain tumours.
A 'simple' method brings success
Until now, it has not been possible to remove and analyse the highly unstable phagosomes from phagocytes in a functional state. Wogram therefore started to develop a new method for phagocytes in cell culture in the laboratory of Prof. Dr. Rudolf Jaenisch at the Whitehead Institute for Biomedical Research in Cambridge, USA, which Jaenisch then further developed in Freiburg in order to also analyse phagosomes in human brain samples.
The method is as simple as it is elegant: in the first step, the phagocytes are opened and the phagosomes are bound to magnetic beads with antibodies. In the second step, the bound beads together with the phagosomes are isolated with a magnet, washed and finally analysed. "The whole process takes just half an hour, which is crucial to ensure that the phagosomes remain intact and their contents are not digested before being analysed," says Wogram.
Link to tumour growth and Alzheimer's disease
"We have already been able to show with the new method that, in addition to removing cell debris and Alzheimer's plaques, the phagosomes also remove superfluous or damaged connections between nerve cells. For the first time, we were able to understand exactly which structures are degraded," says Wogram. This opens up new ways to better understand the role of these cells in learning processes and diseases such as Alzheimer's.
The new method also enabled the researchers to measure differences between phagosomes in healthy tissue and in tumour tissue. They found that phagosomes in tumour tissues contained unusually high amounts of quinolinic acid, which can be used for metabolism in the brain but can also damage nerve cells.
"The exciting thing is that phagocytes in the brain are the only cells that can produce quinolinic acid and store or degrade it in the phagosome. While quinolinic acid can damage nerve cells in Alzheimer's disease, it is thought to promote the growth and spread of brain tumours," says Wogram.
The phagosome therefore has an important role to play: it can influence the course or even the development of incurable brain diseases. "Once we have a better understanding of how phagosomes control the redistribution of quinolinic acid, we may have a new approach to treating Alzheimer's disease or brain tumours," says Wogram.
