Related Experiment Video
Updated: Oct 12, 2025
Dissecting Cell-Autonomous Function of Fragile X Mental Retardation Protein in an Auditory Circuit by In Ovo Electroporation
Published on: July 6, 2022
Altered inflammatory response in FMRP-deficient microglia
Jennifer M Parrott1, Thomas Oster1, Hye Young Lee1
1The Department of Cellular and Integrative Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Abstract:
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.
Insights
Fragile X syndrome (FXS) involves genetic and environmental factors. FXS microglia show heightened inflammation and immune responses when exposed to LPS, indicating a gene-environment interaction.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Fragile X syndrome (FXS) is an inherited intellectual disability often co-occurring with autism spectrum disorders.
- Genetic factors in FXS may increase susceptibility to environmental influences that worsen symptoms.
- The interaction between genetic and environmental risk factors in FXS is not well understood.
Purpose of the Study:
- To investigate the interaction between Fragile X syndrome genetics and environmental factors, specifically inflammation.
- To examine the role of microglia, the brain's immune cells, in this gene-environment interaction.
Main Methods:
- Utilized Fmr1 knock-out (KO) mice, a model for FXS.
- Administered lipopolysaccharide (LPS), an immune stimulus, to Fmr1 KO and wild-type (WT) microglia.
- Assessed inflammatory and phagocytic responses, mitochondrial function, and morphology.
Main Results:
- Fmr1 KO microglia exhibited elevated pro-inflammatory and phagocytic responses to LPS compared to WT microglia.
- Baseline differences in mitochondrial function and morphology were observed between Fmr1 KO and WT microglia.
- LPS treatment exacerbated these mitochondrial differences in Fmr1 KO microglia.
Conclusions:
- Fmr1 KO microglia display an altered inflammatory mechanism.
- These findings suggest a significant gene and environment interaction in the context of Fragile X syndrome.
- Microglia play a crucial role in the exacerbated inflammatory response observed in the FXS model.
