Microglia assume different characteristics at different stages of chronic-relapsing experimental autoimmune encephalomyelitis, a model of secondary progressive multiple sclerosis (MS), according to a new study published in Glia. They also show a particularly mixed phenotype in the chronic stage of encephalomyelitis. 

According to the authors of the study, understanding the properties of microglia can help better understand its role in secondary progressive MS and “aid the development of therapies for this phase of the disease.”

The role of microglia in MS is not well understood. 


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Using morphometric and RNA sequencing analyses, researchers led by Susanne M. Kooistra, PhD, from the Department of Biomedical Sciences of Cells & Systems at the University Medical Center Groningen in The Netherlands characterized microglia in the different phases of chronic-relapsing experimental autoimmune encephalomyelitis.

They showed that in the initial, acute inflammation phase of encephalomyelitis, microglia acquire a proinflammatory phenotype. 

During the remission phase, on the other hand, the expression of standard immune activation genes decreases and the expression of genes associated with tissue remodeling and lipid metabolism increases. 

Finally, in the chronic phase, microglia partially regain inflammatory gene sets and raise the expression of genes tied to proliferation. 

Future work will involve single-cell RNA sequencing for chronic phase experimental autoimmune encephalitis microglia and other immune cells to clarify the processes underlying the slow deterioration that occurs during this phase, the authors said.

MS is the most common type of neurodegenerative disease of the central nervous system affecting young adults. The exact cause of the disease is not known, but it is characterized by the immune system mistakenly attacking the myelin sheath around the nerve cells, causing damage and symptoms such as fatigue, muscle weakness, mobility issues, pain, cognitive dysfunction, and anxiety and depression.

Microglia are located throughout the brain and spinal cord, acting as the first and main form of active immune defense in the central nervous system.

Reference

Vainchtein ID, Alsema AM, Dubbelaar ML, et al. Characterizing microglial gene expression in a model of secondary progressive multiple sclerosis. Glia. Published online November 15, 2022. doi:10.1002/glia.24297