Maresin-1 promotes neuroprotection in relapsing remitting mouse model of multiple sclerosis

Multiple sclerosis (MS) is a prevalent inflammatory neurodegenerative disease in young people, causing neurological abnormalities and impairment. We investigated the effect of maresin 1 (MaR1) on the progression of disease in relapsing remitting form of experimental autoimmune encephalomyelitis (RR-EAE). Treatment with MaR1 in RR-EAE accelerated inflammation resolution, protected against neurological impairments, and delayed disease development by reducing immune cell infiltration (CD4+IL17+ and CD4+IFNg+) into the CNS. Furthermore, injection of MaR1 enhanced IL-10 production, primarily in macrophages and CD4+ cells. However, neutralizing IL-10 with an anti-IL-10 antibody eliminated MaR1's protective impact on RR-EAE, implying that IL-10 plays a role in MaR1's EAE protection. Metabolism is increasingly being recognized as a critical element controlling the effector activity of many immune cells. Our investigation found that, when compared to vehicle treatment, MaR1 administration significantly repaired the metabolic dysregulation seen in CD4+ cells, macrophages, and microglia in the treated group. Furthermore, MaR1 treatment restored defective efferocytosis in EAE mice, which was potentially facilitated by the induction of metabolic alterations in macrophages and microglia. MaR1 also preserved myelin in the EAE group and regulated O4+ oligodendrocyte metabolism by reversing metabolic dysregulation via increased mitochondrial activity and decreased glycolysis. Overall, in a preclinical MS animal model, MaR1 therapy has anti-inflammatory and neuroprotective properties. It also induced metabolic reprogramming in disease-associated cell types, increased efferocytosis, and maintained myelination. These findings suggest MaR1's potential as a novel therapeutic agent for MS and other autoimmune diseases Overall design: To investigate the role of MaR1 in preclinical animal model of multiple sclerosis (EAE), the SJL model was used. We then performed RNA-seq gene expression profiling analysis using data obtained from RNA-seq of CFA, EAE, and MaR1.