Arhgef7 as a key target for enriched environment rescuing spatial cognitive deficits and anxiety-like behaviors in a mouse model of Alzheimer’s disease following early social isolation

作者：Yimiao Wang, Ze Wang, Yue Li, Min Cao, Shuying Zhang, Shixin Ding, Sijia Chen, Yuxi Jin, Yanli Zhang, Junying Gao, Ming Xiao · 发表于：Alzheimer s Research & Therapy · 年份：2025 · DOI：10.1186/s13195-025-01797-5 · 被引用次数：3 · 研究领域：Alzheimer's disease research and treatments、Neurogenesis and neuroplasticity mechanisms、Tryptophan and brain disorders

BACKGROUND: Both social and physical environmental factors influence the progression of Alzheimer's disease (AD), but the underlying mechanisms are not yet fully understood. This study aims to investigate how an enriched environment (EE) alleviates the detrimental effects of early social isolation (SI) on AD-like pathophysiology. METHODS: Four-week-old 5×FAD transgenic mice were randomly divided into group-housed and isolated groups. After 3 weeks, the mice were further raised in either a physical EE or a standard environment for an additional 3 weeks. Subsequently, these experimental subjects underwent a two-week of behavioral tests while maintaining their original housing conditions unchanged, followed by neuropathological analyses. A series of experiments were conducted on the medial prefrontal cortex (mPFC), including transcriptome sequencing, cellular localization, and knockdown and overexpression of a candidate gene, to identify the key molecules through which physical EE alleviates SI-induced AD-like alterations. The protective effects of the identified gene on cultured forebrain neurons exposed to β-amyloid stimulation, as well as its associated signaling pathways, were also investigated. RESULTS: EE enhanced cognitive function and alleviated anxiety-like behavior in SI-5×FAD mice, partially reversing dendritic and synaptic loss and glial cell activation in the mPFC. However, it did not mitigate deficits in social and cooperative behaviors, hypomyelination, or β-amylo...