Characterizing microglial gene expression in a model of chronic-relapsing EAE

Multiple sclerosis (MS) is the most common inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. Chronic-relapsing experimental autoimmune encephalomyelitis (crEAE) in Biozzi ABH mice is an experimental model of MS. This crEAE model is characterized by an acute phase with severe neurological disability, followed by remission of disease, relapse of neurological disease and remission that eventually results in a chronic progressive phase that mimics the secondary progressive phase (SPEAE) of MS. In both MS and the SPEAE the role of microglia is poorly defined. We used the crEAE model to characterize microglia in the different phases of crEAE phases using morphometric and RNA sequencing analyses. At the initial, acute inflammation phase, microglia acquired a pro-inflammatory phenotype. At remission phase, expression of standard immune activation genes was decreased while expression of genes associated with lipid metabolism and wound healing was increased. Chronic phase microglia partially regain inflammatory gene sets and increase expression of genes associated with proliferation. Together, the data presented here indicates that microglia obtain different features at different stages of crEAE and a particularly mixed phenotype in the chronic stage. Understanding the properties of microglia that are present at the chronic phase of EAE may help understand the role of microglia in progressive neurological disease to better aid the development of therapies for secondary progressive MS. Microglia were sorted from the spinal cord by FACS-gating CD11b-postive, CD45-intermediate, and Ly-6C-negative cell populations. RNA-sequencing was performed for microglia from 3 control mice, 3 crEAE mice in acute phase, 3 crEAE mice in remission phase and 3 crEAE mice in chronic phase.