Ultrasound neuromodulation ameliorates chronic corticosterone-induced depression- and anxiety-like behaviors in mice
Canwen Wu, Jiaru He, Yiyue Zhu, Junwei Wu, Yan Chen, Maodan Yuan, Zhongwen Cheng, Lvming Zeng, Xuanrong Ji
Journal of Neural Engineering 2023 · 10.1088/1741-2552/acdea9
Abstract
Objective. Monoamine dysfunction has been implicated as a pathophysiological basis of several mental disorders, including anxiety and depression. Transcranial ultrasound stimulation (TUS) is a noninvasive nerve stimulation technic showing great potential in treating depression/anxiety disorders. This study aims to investigate whether TUS can ameliorate depression with anxiety in mice by regulating brain monoamine levels. Approach. Mice received repeated subcutaneous injections of corticosterone (CORT, 20 mg kg -1 ) for 3 weeks to produce depression- and anxiety-like behaviors. Ultrasound stimulated the dorsal lateral nucleus (DRN) for 30 min daily for 3 weeks without interruption of CORT injection. Behavioral phenotypes of depression and anxiety were estimated by sucrose preference test (SPT), tail suspension test (TST), and elevated plus-maze test (EPM). Liquid chromatography-mass spectrometry (LC-MS) was used to quantify brain levels of serotonin (5-HT), norepinephrine (NE), and dopamine (DA). Western blotting was performed to detect brain-derived neurotrophic factor (BDNF) levels in hippocampal. Main results. TUS of DRN significantly ameliorated the depression-like behaviors in SPT ( p = 0.0004) and TST ( p = 0.0003) as well as anxiety-like behaviors in EPM (open arm entry frequencies, p p = 0.0127) and induced no tissue damage. LC-MS results showed TUS of DRN resulted in a non-significant increase in the 5-HT levels and a significant decrease in the NE levels, but did not affect the levels of DA and BDNF. Significance. These results suggest TUS of DRN has safely and effectively ameliorated CORT-induced depression- and anxiety-like behaviors, possibly by restoring brain levels of 5-HT and NE. TUS may be a safe and effective technique for remedying depression and anxiety comorbidity.
Abstract via europepmc.
Exposures
Exposure 1: TUS of dorsal raphe nucleus, 30 min daily for 3 weeks
Target: raphe nuclei — “dorsal lateral nucleus (DRN)”
Device: custom-built · homemade miniature power ultrasound transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,100 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 315 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 283 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Isppa, domain unspecified (W/cm²) | 2.42 | ✓✓✓⚑ |
1 s stimulation duration with 1 s inter-stimulus interval, repeated for 30 min daily from week 4 to week 6 in freely behaving mice.
Flags from extraction
n_subjects— 24 = Vehicle 8 + Cort 16 (8 CORT, 8 CORT+TUS); separate c-Fos (n=3 TUS) and other cohorts also exist; only 8 behavioural mice received TUS.exposures[0].unspecified_domain.isppa_w_cm2— Isppa given without stating domain; follows the with/without-skull pressures.exposures[0].in_situ.pressure_kpa— Pressure with skull measured by hydrophone through a mouse skull; treated as in_situ measurement.auditory_control— Paper says aural effects should be checked in future research; no control used.exposures[0].target.label— Abstract calls the target the 'dorsal lateral nucleus (DRN)' while the rest of the text says dorsal raphe nucleus.