摘要：SummaryFragile X syndrome (FXS) is an inherited intellectual disability with a high risk for comorbid autism spectrum disorders. Since FXS is a genetic disease, patients are more susceptible to environmental factors aggravating symptomatology. However, this confounding interaction between FXS environmental and genetic risk factors is under-investigated. Here,Fmr1knock-out (KO) mice and the immune stimulus lipopolysaccharide (LPS) were used to explore this interaction between FXS development and inflammation in microglia, the brain’s primary immune cell. Our results demonstrate thatFmr1KO and wild-type (WT) microglia are not different in inflammatory outcomes without LPS. However,Fmr1KO microglia produces an elevated pro-inflammatory and phagocytic response following LPS treatment when compared to WT microglia. Our experiments also revealed baseline differences in mitochondrial function and morphology between WT andFmr1KO microglia, which LPS treatment exaggerated. Our data suggest an altered inflammatory mechanism inFmr1KO microglia implicating a gene and environment interaction.Graphical abstractDisplay OmittedHighlights•Fmr1KO microglia display elevated LPS-induced pro-inflammatory gene expressions•Fmr1KO microglia display elevated LPS-induced pro-inflammatory cytokine releases•Fmr1KO microglia demonstrate increased LPS-induced phagocytic responses•Fmr1KO microglial mitochondria have altered properties and LPS-stimulated responsesMolecular biology; Neuroscience; Immunology
