Single-cell transcriptomics of multiple brain regions in ME/CFS

Project description

This project aims to get a more complete picture of the molecular and cellular changes in ME/CFS. The researchers look at multiple brain areas that may have been affected by ME/CFS and link them to molecular changes in specific cell types. They also want to investigate immune changes in the central nervous system and the periphery. For example, the researchers hope to find new points of grip, which can serve as biomarkers or for the development of new treatments for people with ME/CFS.

The project uses the ME/CFS brain donations from the Dutch Brain Bank. Inclusion takes place on the basis of a diagnosis during life by a treating physician or medical specialist. The project has two main objectives:

1) In-depth characterisation of changes in the expression of genes in brain cells

Within the first part of the project, three brain areas that may have been affected by ME/CFS are analysed in great detail. These brain areas, namely the hippocampus, frontal cortex and hypothalamus, have been selected because ME/CFS symptoms may be related to these brain areas. A special technique called single nucleus RNA sequencing (snRNA-seq) is used to identify changes in cell types and their activity in these brain areas.

2) Profiling of immune compartments in ME/CFS

Earlier research by the scientists shows that there are noticeable changes in the microglia. These are special immune cells in the brain. These changes are mainly observed in different parts of the brain in people with ME/CFS. This may indicate a disturbance of the immune cells in the brain and possibly also in the body. Within the second part of the project, this relationship is investigated in more detail and findings in the brain are compared with those from the project of Niels Eijkelkamp on immune cells in the blood of ME/CFS patients. This is done to map overlaps in changes in the peripheral immune system (blood) and in the brain. For example, the researchers hope to find overlapping targets that can serve as biomarkers or when developing new treatments for people with ME/CFS.

The researchers expect changes to occur in the immune system and in the brains of people with ME/CFS. By making a detailed and cell-specific overview for the first time of all (molecular) brain changes in ME/CFS, the research team expects to identify molecular and cellular causes for ME/CFS-specific symptoms. The results should also contribute to a better understanding of the role of both the peripheral and central immune system in ME/CFS and may contribute to future treatment options for ME/CFS. 

Description adapted from project website: see link above.