CXCL10 impairs synaptic plasticity was modulated by cGAS-STING pathway after stroke in mice

Sensorimotor deficits following stroke remain a major cause of disability, but little is known about the specific pathological mechanisms. Exploring the pathological mechanisms and identifying potential therapeutic targets to promote functional rehabilitation after stroke are essential. CXCL10, also known as interferon-gamma-inducible protein 10 (IP-10), plays an important role in multiple brain disorders by mediating synaptic plasticity, yet its role in stroke is still unclear. In this study, mice were treated with photothrombotic stroke, and sensorimotor deficits were determined by the ladder walking tests, tape removal tests, and rotarod tests. The density of dendritic spines and synaptic plasticity was evaluated by Thy1-EGFP mice and electrophysiology. We found that photothrombotic stroke induced sensorimotor deficits and upregulated the expression of CXCL10, whereas suppressing the expression of CXCL10 by adeno-associated virus (AAV) ameliorated sensorimotor deficits and increased the levels of synapse-related proteins, the density of dendritic spines and synaptic strength. Furthermore, the cGAS-STING pathway was activated by stroke and induced CXCL10 release, and cGAS or STING antagonists downregulated the levels of CXCL10 and improved synaptic plasticity after stroke. Collectively, our results indicate that cGAS-STING pathway activation promoted CXCL10 release and impaired synaptic plasticity during stroke recovery.