ArticleCNS neuroscience & therapeutics2026
Low-Intensity Pulsed Ultrasound Alleviation of LPS-Induced Depression-Like Behavior via Microglial P2X4R Inhibition and BDNF/TrkB Pathway Activation.
Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Low-Intensity Pulsed Ultrasound Alleviation of LPS-Induced Depression-Like Behavior via Microglial P2X4R Inhibition and BDNF/TrkB Pathway Activation.CNS neuroscience & therapeutics · 2026Article
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Authors and funding
10 authors.
Funding
Abstract
objectiveLow-intensity pulsed ultrasound (LIPUS) shows promising anti-inflammatory and neuroprotective effects for different types of neurological disorders. This study aims to investigate the therapeutic effects of LIPUS on LPS-induced depression-like behavior and neuroinflammation and to elucidate the underlying molecular mechanisms.
methodsA depressive mouse model is established by intraperitoneal injection of LPS (1.0 mg/kg/day for 7 days). LIPUS is applied to the hippocampal region (30 min/day). Behavioral assessments include the open field test (OFT), forced swim test (FST), and tail suspension test (TST). Molecular analyses, including Western blotting, immunofluorescence, and qPCR, are performed to evaluate the expression of P2X4R, IBA1, inflammatory cytokines (IL-1β, IL-6, TNF-α), BDNF/TrkB signaling pathway, and apoptosis-related proteins (Bax, Bcl-2). The involvement of P2X4R is further examined using ivermectin (IVM), a selective P2X4R agonist.
resultsLIPUS significantly alleviates the LPS-induced depression-like behavior, suppresses hippocampal pro-inflammatory cytokine expression, inhibits microglial activation, and reduces neuronal apoptosis. Mechanistically, LIPUS downregulates P2X4R and IBA1, upregulates BDNF protein levels and TrkB phosphorylation, and modulates the Bax and Bcl-2 expression. Co-localization studies confirm that P2X4R is predominantly expressed in microglia, and LIPUS markedly reduces the overlap. Notably, the anti-inflammatory, neuroprotective, and antidepressant effects of LIPUS are significantly attenuated by IVM, highlighting the critical role of P2X4R suppression in mediating therapeutic effects.
conclusionLIPUS mitigates LPS-induced neuroinflammation, neuronal apoptosis, and depression-like behavior by targeting microglial P2X4R and activating the BDNF/TrkB pathway. The findings provide mechanistic insights and demonstrate that LIPUS is a promising non-pharmacological intervention for depression, underscoring the translational potential of P2X4R as a therapeutic target.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.