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Altered inflammatory response in FMRP-deficient microglia


ABSTRACT: Summary Fragile 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, Fmr1 knock-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 that Fmr1 KO and wild-type (WT) microglia are not different in inflammatory outcomes without LPS. However, Fmr1 KO 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 and Fmr1 KO microglia, which LPS treatment exaggerated. Our data suggest an altered inflammatory mechanism in Fmr1 KO microglia implicating a gene and environment interaction. Graphical abstract Highlights • Fmr1 KO microglia display elevated LPS-induced pro-inflammatory gene expressions• Fmr1 KO microglia display elevated LPS-induced pro-inflammatory cytokine releases• Fmr1 KO microglia demonstrate increased LPS-induced phagocytic responses• Fmr1 KO microglial mitochondria have altered properties and LPS-stimulated responses Molecular biology; Neuroscience; Immunology

SUBMITTER: Parrott J 

PROVIDER: S-EPMC8602000 | biostudies-literature |

REPOSITORIES: biostudies-literature

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