MALAT1 promotes microglia activation and neuronal apoptosis through via the miR-124-3p/ SGK1 axis mediating experimental autoimmune encephalomyelitis disease progression in mice

Multiple sclerosis (MS) significantly impairs quality of life due to its high disability rate. Recent research indicates that the long non-coding RNA Malat1 is specifically upregulated in MS and is critically involved in mediating neuroinflammatory responses and microglial activation. This study explores the function and mechanism of the Malat1/miR-124-3p/Sgk1 pathway in MS and microglia activation. Initially, the study established an experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice using MOG35-55. Subsequently, it confirmed a correlation between the expression of Malat1 in the L5 spinal cord and disease progression and microglia numbers. Further, cell transfection and lentiviral infection of BV2 microglia were performed, followed by an assessment of interactions within the Malat1/miR-124-3p/Sgk1 pathway. Western blotting was used to detect changes in CD68 and I kappa B alpha/NF kappa B phosphorylation, key indicators of microglia activation. Furthermore, coincubation of BV2 and HT-22 mouse hippocampal neuronal cells revealed that increased Malat1 expression enhances BV2's role in promoting HT-22 cell apoptosis under 200 ng/mL LPS. Both miR-124-3p inhibition and Sgk1 overexpression replicated these effects. Dual luciferase reporter assays confirmed that Malat1 absorbed miR-124-3p to upregulate Sgk1 expression. Malat1 overexpression in EAE mice led to an increase in TUNELpositive cells and upregulated CD68 and phosphorylated I kappa B alpha/NF kappa B proteins. Conversely, intrathecal silencing of Malat1 reduced these protein expression changes. This study elucidates Malat1's role in MS, offering critical insights for developing future therapeutic strategies.