Scholarlink

<p>Autism spectrum disorder (ASD) pathophysiology often involves striatal dysfunction, yet the underlying mechanisms remain unclear. Mutations in Forkhead box G1 (<i>FOXG1</i>) cause FOXG1 syndrome, a condition sharing core ASD features. Here, loss of <i>Foxg1</i> in the indirect pathway spiny projection neurons (iSPNs) in mice recapitulates ASD symptoms, including social, language, and fine movement deficits. <i>Foxg1</i> deficiency causes dendritic simplification, spine reduction, and impairs excitatory synaptic transmission. Transcriptome reveals that FOXG1 drives gene networks to multidimensionally control synaptic functions from spine morphogenesis, synaptic maturation, ion transmembrane transport, glutamate receptor clustering, to neurotransmitter release and synaptic transmission. Importantly, FOXG1 directly activates the transcription of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, and pharmacological potentiation of AMPAR activity normalizes synaptic function and rescues behavioral deficits. Our study provides a new perspective on the relationship between FOXG1 and ASD etiology in iSPNs and suggests the potential of AMPAR activation as a therapeutic intervention for ASD and FOXG1 Syndrome.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

FOXG1 Hierarchically Shapes Synaptic Functions in Striatal iSPNs and Contributes to ASD Etiology

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月2日

查看全文
  • Baoshen Zhang,
  • Daxiang Xu,
  • Shuangshuang Dong,
  • Pei Zhu,
  • Pengfei Jiang,
  • Jie Sun,
  • Junhua Liu,
  • Huanxin Chen,
  • Chunjie Zhao

摘要

Autism spectrum disorder (ASD) pathophysiology often involves striatal dysfunction, yet the underlying mechanisms remain unclear. Mutations in Forkhead box G1 (FOXG1) cause FOXG1 syndrome, a condition sharing core ASD features. Here, loss of Foxg1 in the indirect pathway spiny projection neurons (iSPNs) in mice recapitulates ASD symptoms, including social, language, and fine movement deficits. Foxg1 deficiency causes dendritic simplification, spine reduction, and impairs excitatory synaptic transmission. Transcriptome reveals that FOXG1 drives gene networks to multidimensionally control synaptic functions from spine morphogenesis, synaptic maturation, ion transmembrane transport, glutamate receptor clustering, to neurotransmitter release and synaptic transmission. Importantly, FOXG1 directly activates the transcription of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, and pharmacological potentiation of AMPAR activity normalizes synaptic function and rescues behavioral deficits. Our study provides a new perspective on the relationship between FOXG1 and ASD etiology in iSPNs and suggests the potential of AMPAR activation as a therapeutic intervention for ASD and FOXG1 Syndrome.