Low-intensity pulsed ultrasound modulating neuroinflammation by hippocampal gene expression in LPS-induced depression

Background: Neuroinflammation is critically implicated in the pathogenesis of depression. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive neuromodulation technique with therapeutic potential, though its molecular mechanisms in depression remain unclear. Objective: This study aims to elucidate the transcriptomic mechanisms underlying the effects of LIPUS in the hippocampus of lipopolysaccharide (LPS)-induced depressed mice. Methods: We established an LPS-induced mouse model of depression and applied LIPUS to the hippocampus. Hippocampal transcriptomes were profiled by RNA-seq, and bioinformatic analyses identified key biological processes, pathways, and hub genes. Results: LIPUS significantly reverses LPS-induced transcriptomic alterations. Enrichment analysis reveals that LIPUS modulated pathways are related to neuroinflammation and synaptic plasticity. Protein-protein interaction network analysis further identifies central hub genes governing these processes. Conclusion: Our findings demonstrate that LIPUS mitigates depression-like phenotypes by reprogramming the hippocampal transcriptome, primarily through targeting neuroinflammatory and synaptic plasticity networks, revealing its potential as a novel therapeutic strategy. © 2026 Elsevier Inc.