Parrott Jennifer M, Oster Thomas, Lee Hye Young
The Department of Cellular and Integrative Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
iScience. 2021 Oct 15;24(11):103293. doi: 10.1016/j.isci.2021.103293. eCollection 2021 Nov 19.
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, 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 KO and wild-type (WT) microglia are not different in inflammatory outcomes without LPS. However, 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 KO microglia, which LPS treatment exaggerated. Our data suggest an altered inflammatory mechanism in KO microglia implicating a gene and environment interaction.
脆性X综合征（FXS）是一种遗传性智力障碍，合并自闭症谱系障碍的风险很高。由于FXS是一种遗传性疾病，患者更容易受到加重症状的环境因素影响。然而，FXS环境和遗传风险因素之间这种混杂的相互作用尚未得到充分研究。在此，我们使用基因敲除（KO）小鼠和免疫刺激剂脂多糖（LPS）来探究FXS发育与小胶质细胞（大脑主要免疫细胞）炎症之间的这种相互作用。我们的结果表明，在没有LPS的情况下，KO和野生型（WT）小胶质细胞的炎症反应没有差异。然而，与WT小胶质细胞相比，LPS处理后KO小胶质细胞产生了增强的促炎和吞噬反应。我们的实验还揭示了WT和KO小胶质细胞在线粒体功能和形态上的基线差异，LPS处理加剧了这种差异。我们的数据表明KO小胶质细胞中炎症机制发生了改变，这涉及基因与环境的相互作用。
