Researchers have identified immune cells that protect the aging brain
In a recent study published in Nature Communications researchers from CMM discovered a unique subgroup of microglia cells enriched in the aging mouse brain. Augmenting the number of these cells in a mouse model of neuroinflammation resulted in reduced neurological disability. The results present a potential treatment target for age-associated neuroinflammatory diseases, such as progressive multiple sclerosis.
Microglia are a type of cells found throughout the brain and spinal cord and they act as a first line of immune defense specific for the central nervous system.
“By characterizing cell populations in genetically modified mice under both healthy and neuroinflammatory conditions, we identified a previously undescribed subgroup of microglial cells that was more prominent in aging mice”, says Rasmus Berglund, postdoc in Maja Jagodic’s CMM Group, and first author of the study.
The researchers found that these cells are dependent on the signaling molecule interleukin-34 (IL-34) and on the cellular process known as autophagy, which is crucial for adapting to metabolic and immunological changes and signals. Further characterization of this microglia subpopulation revealed heightened levels of inflammation-associated markers which are common in various neurological diseases.
Interestingly, when the mice were exposed autoimmune neuroinflammation, the reduction in these microglia correlated with an increased mortality. Conversely, augmenting the number of these microglia by stimulating them with IL-34 mitigated the impact of neuroinflammation, reducing neurological disability in the mice. This implies a positive role for these inflammatory cells in promoting health.
These findings present a promising treatment option for bolstering the microglia population in age-associated neuroinflammatory diseases, such as progressive multiple sclerosis, which currently lack viable treatment alternatives.
To validate their research in connection with human disease, Rasmus Berglund and colleagues will study cytokine profiles in cerebrospinal fluids and analyze post-mortem brain tissue. They are also launching a project to create a drug screening pipeline using stem cell-derived microglia from both healthy donors and people with multiple sclerosis. Their aim is to identify compounds that improve the health-promoting capacity of microglia and find biomarkers linked to this improved state for better prognosis. By doing this, they hope to advance our understanding of multiple sclerosis as well as other age-associated neurological diseases
Funding
The project was supported by grants from the Swedish Research Council, the Swedish Brain Foundation, Margaretha af Ugglas foundation, Stockholm County Council (ALF), SSMF, Neuroförbundet, Chinese Scholarship Council (CSC), Knut and Alice Wallenberg Foundation and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme.
Publication
Berglund R, Cheng Y, Piket E, Z Adzemovic M, Zeitelhofer M, Olsson T, Ortlieb Guerreiro-Cacais A, Jagodic M. The aging mouse CNS is protected by an autophagy-dependent microglia population promoted by IL-34. Nat Commun. 2024 Jan 9;15(1):383. doi: 10.1038/s41467-023-44556-6.