Low-intensity pulsed ultrasound modulating neuroinflammation by hippocampal gene expression in LPS-induced depression
Yuanli Wang, Lijie Zhang, Linxian Li, Jingjie Wang, Mingxue Wang, Nannan Huang, Paul K. Chu, Hongrui Zhan, Chengbiao Ding
Gene Reports 2026, 42, 102431 · 10.1016/j.genrep.2026.102431
rodentdepressionsystemic inflammationbehaviourhistology molecular
Speciesmouse (C57BL/6J)
Subjects8 animals
Sessions per subject7
Randomisedyes
Blindingnot reported
Sham / controlno treatment control
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsbehaviour, histology molecular — Open Field Test; Forced Swimming Test; Tail Suspension Test; body weight; eyelid ptosis score; Nissl staining; hippocampal BDNF immunofluorescence; hippocampal RNA-seq transcriptome (KEGG/GO/PPI analysis); qRT-PCR validation of hub genes (Fn1, C3, Fcgr2b, Lcn2, Itgb2)
Direction of effectnot assessedThe study did not directly measure neuronal excitation/inhibition; LIPUS reversed LPS-induced depressive-like behaviors (reduced immobility in FST/TST, restored locomotion and body weight, reduced eyelid ptosis), restored hippocampal BDNF expression, and partially reversed LPS-induced hippocampal transcriptomic changes (reduced expression of inflammatory hub genes Fn1, C3, Fcgr2b, Lcn2, Itgb2).
Adverse eventsnone observedNeurons in the CA1 region were arranged in an orderly manner across the control, LPS, and LIPUS groups, without evidence of neuronal loss or structural damage; these findings indicate that under the present experimental conditions, LIPUS did not cause detectable tissue injury in the mouse brain.
Exposures
Exposure 1: LIPUS to the hippocampus in LPS-induced depression model
Target: hippocampus — “hippocampus”
Device: other named manufacturer · ZK-JLCS-8601 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 800 | ✓✓✓ |
| Pulse duration (ms) | 5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 60 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Protocol, in the paper’s words
Pulsed ultrasound was delivered via a conical collimator (total length ~9 mm, upper inner diameter 14 mm, terminal diameter 5 mm) filled with degassed water, coupled to the skull over the hippocampal target under isoflurane anesthesia. In the LIPUS group, mice received daily intraperitoneal LPS injection followed immediately by a 15-minute LIPUS treatment, once daily for 7 consecutive days.
Flags from extraction
exposures[0].timing.sonication_duration_s— Methods state a 'stimulation duration of 60 s' per sonication train but also describe a '15 min LIPUS treatment' given daily; the paper does not clarify how the 60 s train relates to the 15 min daily session (e.g. repeated trains), so both durations are noted in protocol_description.exposures[0].device.manufacturer— Paper names the device model (ZK-JLCS-8601) and only gives 'Jiangsu, China' as location, not a manufacturer/company name.direction_of_effect— No direct measure of neuronal excitation/inhibition (e.g. electrophysiology or immediate-early gene marker) was made; classified as not_assessed.sham_type— Control and LPS-only groups received no ultrasound device or sham procedure at all (only injections); classified as no_treatment_control.