Transcranial ultrasound stimulation relieves depression in mice with chronic restraint stress

Zhu, Yiyue; He, Jiaru; Wu, Canwen; Wu, Jyh‐Horng; Cheng, Zhongwen; Chen, Yan; Yuan, Maodan; Zeng, Lvming; Ji, Xuanrong

doi:10.1088/1741-2552/ac8bfd

Cited by 8 publications

(10 citation statements)

References 71 publications

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“…Tryptophan is the sole precursor of 5-HT, which is an important monoamine neurotransmitter. Many studies have reported that the level of 5-HT was significantly decreased in depression Zhu et al, 2022). Our previous studies also found the significantly decreased level of 5-HT in depression patients' plasma and brain areas of depressed mice (Wu et al, 2020;Tian et al, 2022;Xie et al, 2023).…”

Section: B a Figuresupporting

confidence: 55%

Tryptophan metabolism as bridge between gut microbiota and brain in chronic social defeat stress-induced depression mice

Xie

Wu²,

Chen³

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundsGut microbiota plays a critical role in the onset and development of depression, but the underlying molecular mechanisms are unclear. This study was conducted to explore the relationships between gut microbiota and host’s metabolism in depression.MethodsChronic social defeat stress (CSDS) model of depression was established using C57BL/6 male mice. Fecal samples were collected from CSDS group and control group to measure gut microbiota and microbial metabolites. Meanwhile, tryptophan metabolism-related metabolites in hippocampus were also analyzed.ResultsCSDS successfully induced depressive-like behaviors in CSDS group. The 24 differential bacterial taxa between the two groups were identified, and 14 (60.87%) differential bacterial taxa belonged to phylum Firmicutes. Functional analysis showed that tryptophan metabolism was significantly affected in CSDS mice. Meanwhile, 120 differential microbial metabolites were identified, and two key tryptophan metabolism-related metabolites (tryptophan and 5-hydroxytryptophan (5-HTP)) were significantly decreased in feces of CSDS mice. The correlation analysis found the significant relationships between tryptophan and differential bacterial taxa under Firmicutes, especially genus Lactobacillus (r=0.801, p=0.0002). In addition, the significantly decreased 5-hydroxytryptamine (5-HT) in hippocampus of depressed mice was also observed.ConclusionsOur results showed that tryptophan metabolism might have an important role in the crosstalk between gut microbioa and brain in depression, and phylum Firmicutes, especially genus Lactobacillus, might be involved in the onset of depression through regulating tryptophan metabolism.

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Section: B a Figuresupporting

confidence: 55%

Tryptophan metabolism as bridge between gut microbiota and brain in chronic social defeat stress-induced depression mice

Xie

Wu²,

Chen³

et al. 2023

Front. Cell. Infect. Microbiol.

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“…However, the maximum ultrasound pressure of the transducer is only 300 kPa, which is difficulty to open the BBB. The ultrasound pressure required for some ultrasound neuromodulation experiments is more than 300 kPa [57,58], which is difficult to meet. The system developed in this study can achieve a maximum ultrasound pressure of 1.8 MPa while generating bifocal ultrasound.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous multi-target ultrasound neuromodulation in freely-moving mice based on a single-element ultrasound transducer

He¹,

Zhu²,

Wu³

et al. 2023

J. Neural Eng.

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Objective: Ultrasound neuromodulation has become an emerging method for the therapy of neurodegenerative and psychiatric diseases. The phased array ultrasonic transducer enables multi-target ultrasound neuromodulation in small animals, but the relatively large size and mass and the thick cables of the array limit the free movement of small animals. Furthermore, spatial interference may occur during multi-target ultrasound brain stimulation with multiple micro transducers. Approach: In this study, we developed a miniature power ultrasound transducer and used the virtual source time inversion method and 3-D printing technology to design, optimize, and manufacture the acoustic holographic lens to construct a multi-target ultrasound neuromodulation system for free-moving mice. The feasibility of the system was verified by in vitro transcranial ultrasound field measurements, in vivo dual-target blood-brain barrier opening experiments, and in vivo dual-target ultrasound neuromodulation experiments. Main results: The developed miniature transducer has a diameter of 4.0 mm, a center frequency of 1.1 MHz, and a weight of 1.25 g. The developed miniature acoustic holographic lens had a weight of 0.019 g to generate dual-focus transcranial ultrasound. The ultrasonic field measurements’ results showed that the bifocal’s horizontal distance was 3.0 mm, the -6 dB focal spot width in the x-direction was 2.5 and 2.25 mm, and 2.12 and 2.24 mm in the y-direction. Finally, the in vivo experimental results showed that the system could achieve dual-target blood-brain barrier opening and ultrasound neuromodulation in freely-moving mice. Significance: The ultrasonic neuromodulation system based on a miniature single-element transducer and the miniature acoustic holographic lens could achieve dual-target neuromodulation in awake small animals, which is expected to be applied to the research of non-invasive dual-target ultrasonic treatment of brain diseases in awake small animals.

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“…Finally, the supernatant was filtered by using a filter membrane, and the filtrate was used for assays. LC and MC analysis conditions are the same as those described in our previous work [13].…”

Section: Lc-ms Analysismentioning

confidence: 99%

“…However, acute optogenetic activation of the DRN increased active stress-coping in rats and mice, and long-term activation of serotonergic neurons might produce a long-term positive stress response [19]. Our prior study indicated that TUS of DRN could improve the depression-like behaviors in depression mice models [13], which suggests that DRN may be one of the effective targets of TUS in treating depression.…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, these therapies are invasive or have relatively low spatial resolution [6,10]. Excitingly, a growing number of studies have demonstrated that transcranial ultrasound stimulation (TUS) with the merits of non-invasiveness, high spatial resolution, and high penetration depth shows great potential for the treatment of MDD and anxiety [11][12][13][14]. However, there are few studies on TUS for depression and anxiety comorbidity.…”

Section: Introductionmentioning

confidence: 99%

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

Zhu

et al. 2023

J. Neural Eng.

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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.

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Transcranial ultrasound stimulation relieves depression in mice with chronic restraint stress

Cited by 8 publications

References 71 publications

Tryptophan metabolism as bridge between gut microbiota and brain in chronic social defeat stress-induced depression mice

Tryptophan metabolism as bridge between gut microbiota and brain in chronic social defeat stress-induced depression mice

Simultaneous multi-target ultrasound neuromodulation in freely-moving mice based on a single-element ultrasound transducer

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

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