1. Academic Validation
  2. Ultrasound neuromodulation ameliorates chronic corticosterone-induced depression- and anxiety-like behaviors in mice

Ultrasound neuromodulation ameliorates chronic corticosterone-induced depression- and anxiety-like behaviors in mice

  • J Neural Eng. 2023 Jun 15. doi: 10.1088/1741-2552/acdea9.
Canwen Wu 1 Jiaru He 1 Yiyue Zhu 1 Junwei Wu 1 Lvming Zeng 1 Yan Chen 1 Maodan Yuan 2 Zhongwen Cheng 1 Xuanrong Ji 2
Affiliations

Affiliations

  • 1 Guangdong University of Technology, Guangzhou 510006, People's Republic of China, Guangzhou, Guangdong, 510006, CHINA.
  • 2 Guangdong University of Technology, Guangzhou 510006, People's Republic of China, Guangzhou, 510006, CHINA.
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) for 3 weeks to produce depression- and anxiety-like behaviors. Ultrasound stimulated the dorsal lateral nucleus (DRN) for 30 minutes 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 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 < 0.05). Moreover, TUS increased c-Fos-positive cell expression (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.

Keywords

anxiety; corticosterone; depression; dorsal raphe nucleus; monoamines dysfunction; transcranial ultrasound stimulation.

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