东南大学赵春杰团队发现了FOXG1影响纹状体iSPN突触功能并参与ASD病因学。这一研究成果于2026年2月2日发表在国际顶尖学术期刊《神经科学通报》上。

自闭症谱系障碍（ASD）的病理生理常涉及纹状体功能障碍，但其潜在机制尚不清楚。叉头框蛋白G1（FOXG1）的突变会导致FOXG1综合征，这是一种共享ASD核心特征的疾病。小鼠间接通路棘投射神经元（iSPNs）中Foxg1的缺失再现了ASD症状，包括社交、语言和精细运动缺陷。。Foxg1缺失会导致树突结构简化、树突棘减少，并损害兴奋性突触传递。转录组分析显示，FOXG1驱动基因网络从多个维度控制突触功能，包括树突棘形态发生、突触成熟、离子跨膜转运、谷氨酸受体簇集，到神经递质释放和突触传递。重要的是，FOXG1直接激活α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）亚基的转录，AMPAR活性的药理学增强可使突触功能正常化并挽救行为缺陷。他们的研究为iSPNs中FOXG1与ASD病因学之间的关系提供了新的视角，并提示AMPAR激活作为ASD和FOXG1综合征的治疗干预的潜力。

附：英文原文

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

Author: Zhang, Baoshen, Xu, Daxiang, Dong, Shuangshuang, Zhu, Pei, Jiang, Pengfei, Sun, Jie, Liu, Junhua, Chen, Huanxin, Zhao, Chunjie

Issue&Volume: 2026-02-02

Abstract: 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.

DOI: 10.1007/s12264-025-01573-3

Source: https://link.springer.com/article/10.1007/s12264-025-01573-3