Fragile X syndrome (FXS) is the most common genetic cause of autism spectrum disorder engendered by transcriptional silencing of the fragile X messenger ribonucleoprotein 1 ( FMR1 ) gene. Given the early onset of behavioral and molecular changes, it is imperative to know the optimal timing for therapeutic intervention. Case reports documented benefits of metformin treatment in FXS children between 2 and 14 y old. In this study, we administered metformin from birth to Fmr1 −/y mice which corrected up-regulated mitogen-2 activated protein kinase/extracellular signal-regulated kinase and mammalian/mechanistic target of rapamycin complex 1 signaling pathways and specific synaptic mRNA-binding targets of FMRP. Metformin rescued increased number of calls in ultrasonic vocalization and repetitive behavior in Fmr1 −/y mice. Our findings demonstrate that in mice, early-in-life metformin intervention is effective in treating FXS pathophysiology.

中文翻译：

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早期二甲双胍治疗：针对脆性 X 综合征病理生理学的有效方法


脆性 X 综合征 (FXS) 是自闭症谱系障碍最常见的遗传原因，由脆性 X 信使核糖核蛋白 1 的转录沉默引起。 FMR1 ）基因。鉴于行为和分子变化的早期发生，必须了解治疗干预的最佳时机。病例报告记录了二甲双胍治疗对 2 至 14 岁 FXS 儿童的益处。在这项研究中，我们从出生到FMR1 -/y小鼠纠正了上调的丝裂原 2 激活蛋白激酶/细胞外信号调节激酶和雷帕霉素复合物 1 信号通路的哺乳动物/机械靶标以及 FMRP 的特定突触 mRNA 结合靶标。二甲双胍挽救了超声发声和重复行为中增加的呼叫数量FMR1 -/y老鼠。我们的研究结果表明，在小鼠中，生命早期二甲双胍干预可有效治疗 FXS 病理生理学。