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Altered inflammatory response in FMRP-deficient microglia
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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602000/ https://www.ncbi.nlm.nih.gov/pubmed/34820601 http://dx.doi.org/10.1016/j.isci.2021.103293 |
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author | Parrott, Jennifer M. Oster, Thomas Lee, Hye Young |
author_facet | Parrott, Jennifer M. Oster, Thomas Lee, Hye Young |
author_sort | Parrott, Jennifer M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8602000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-86020002021-11-23 Altered inflammatory response in FMRP-deficient microglia Parrott, Jennifer M. Oster, Thomas Lee, Hye Young iScience Article 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. Elsevier 2021-10-15 /pmc/articles/PMC8602000/ /pubmed/34820601 http://dx.doi.org/10.1016/j.isci.2021.103293 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Parrott, Jennifer M. Oster, Thomas Lee, Hye Young Altered inflammatory response in FMRP-deficient microglia |
title | Altered inflammatory response in FMRP-deficient microglia |
title_full | Altered inflammatory response in FMRP-deficient microglia |
title_fullStr | Altered inflammatory response in FMRP-deficient microglia |
title_full_unstemmed | Altered inflammatory response in FMRP-deficient microglia |
title_short | Altered inflammatory response in FMRP-deficient microglia |
title_sort | altered inflammatory response in fmrp-deficient microglia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602000/ https://www.ncbi.nlm.nih.gov/pubmed/34820601 http://dx.doi.org/10.1016/j.isci.2021.103293 |
work_keys_str_mv | AT parrottjenniferm alteredinflammatoryresponseinfmrpdeficientmicroglia AT osterthomas alteredinflammatoryresponseinfmrpdeficientmicroglia AT leehyeyoung alteredinflammatoryresponseinfmrpdeficientmicroglia |