Astragaloside IV ameliorates autism-like behaviors in BTBR mice by modulating Camk2n2-dependent OXPHOS and neurotransmission in the mPFC

作者：Mei Chen, Jiahui Shi, Tianyao Liu, Jiayin Liu, Yulong Liu, Jianghui Li, Yi Luo, Jing Luo, Xin Li, Hong Gong, Xiaotang Fan · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.01.030 · 被引用次数：9 · 研究领域：Autism Spectrum Disorder Research、Traditional Chinese Medicine Analysis、Neurogenesis and neuroplasticity mechanisms

Schematic summary of the proposed mechanism underlying the improvements in autistic behaviors observed with ASIV treatment in BTBR mice. • ASIV is beneficial for ASD-like behaviors in BTBR mice. • ASIV takes anti-autism effects via rescuing OXPHOS function and excitatory-inhibitory imbalance in layer V of mPFC. • Camk2n2 mediates the neuroprotective effects of ASIV in the context of ASD. • The Ca 2+ /Camk2/CREB pathway could be a promising therapeutic target for ASD. Autism spectrum disorder (ASD) represents a multifaceted set of neurodevelopmental conditions marked by social deficits and repetitive behaviors. Astragaloside IV (ASIV), a natural compound derived from the traditional Chinese herb Astragali Radix, exhibits robust neuroprotective effects. However, whether ASIV can ameliorate behavioral deficits in ASD remains unknown. This work aimed to determine the efficacy and molecular mechanisms of ASIV in ASD. The autistic BTBR T + tf/J (BTBR) mice were used in this study. Behavioral tests were performed to assess the ASD-like phenotypes. The neurotransmitter levels and synaptic transmission were evaluated by high-performance liquid chromatography and whole-cell patch clamp recordings, respectively. Molecular biological techniques, immunostaining, and RNA-sequencing (RNA-seq) were combined to uncover the underlying molecular mechanisms. Our study showed that both social impairment and repetitive behaviors were significantly improved after ASIV treatment in a dose-dependent ...