Sox10 glial-neuron nuclear communication mediates anti-apoptosis neuroprotection after ischaemic stroke

作者：Maojiao Huang, Xiaoyin Huang, Yunru Chen, Z Zhang, Ju Wang, Qiao Yin, Jiayu Li, Fanbin Xie, Wanting Huang, Falei Yuan, Chunyun Luo, Xiaosong He · 发表于：Stroke and Vascular Neurology · 年份：2026 · DOI：10.1136/svn-2025-004934 · 被引用次数：1 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Cell death mechanisms and regulation、RNA regulation and disease

Background Neuronal apoptosis is a hallmark of ischaemic stroke, yet effective neuroprotective therapies remain scarce. Recent studies suggest that Sox10-lineage cells (SOL) can transfer nuclear material to neurons. However, whether this process contributes to neuronal survival after stroke remains unknown. Methods Sox10-iCreERT2:Ai9 mice subjected to distal middle cerebral artery occlusion (dMCAO) were used to investigate SOL to neuron material transfer after ischaemic injury. High-resolution confocal imaging, AAV-based lineage tracing and single-nucleus RNA sequencing were employed to identify tdTomato-positive neurons and characterise their transcriptional profiles. Behavioural tests and histological analyses were performed to evaluate the neuroprotective effects of tamoxifen treatment. Results A subset of neurons from cortical layer 6 expressed tdTomato protein derived from SOL, suggesting intercellular material transfer. Notably, tdTomato + neurons exhibited enhanced Bcl2 expression. High-dose tamoxifen (160 mg/kg) increased the number of tdTomato + neurons by approximately fourfold compared with low-dose treatment. Correspondingly, the proportion of apoptotic neurons (TUNEL + /NeuN + ) in the high-dose tamoxifen group was reduced from 33.4% to 19.3%, and infarct volume decreased from 11.68% to 7.26% of the ipsilateral hemisphere after ischaemic stroke. Functionally, high-dose tamoxifen significantly improved sensorimotor recovery, as evidenced by faster adhesive removal...