Modulation effects of low-intensity transcranial ultrasound stimulation on the neuronal firing activity and synaptic plasticity of mice

Zhao, Zhe; Ji, Hui; Zhang, Cong; Pei, Jiamin; Zhang, Xiangjian; Yuan, Yi

doi:10.1016/j.neuroimage.2023.119952

Cited by 12 publications

(5 citation statements)

References 58 publications

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“…Furthermore, ultrasonic stimuli can facilitate the regeneration and repair of damaged neurons and the creation of new neurons 3 . Ultrasonic stimulation triggers neuronal activity by activating the synaptic signal cascade 53 , resulting in increased excitatory synaptic transmission 54 , cortical excitability and neuroplasticity 55,56 . C-Fos, a protein widely used as a marker of neuronal activation [57][58][59] , was increased in the LITUS-treated CPR group, particularly in the cerebral cortex and amygdala region.…”

Section: Discussionmentioning

confidence: 99%

Low-intensity transcranial ultrasound (LITUS) exerts neuroprotective effects by modulating inflammatory responses via the Piezo1-Dkk3/Ca 2+ /PI3K-Akt signaling pathway

Xu,

Gu,

Liu

et al. 2024

Preprint

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Background Post-cardiac arrest brain injury (PCABI) contributes to unfavorable outcomes following cardiopulmonary resuscitation (CPR) significantly, with effective therapeutic interventions for PCABI remain elusive. Low-intensity transcranial ultrasound (LITUS) has exhibited neuroprotective effects in various disease models, yet the precise mechanisms underlying these effects have not been fully elucidated. Consequently, the therapeutic potential of ultrasound stimuli in PCABI and the underlying mechanisms necessitate further exploration. Methods In vivo, a murine model of cardiac arrest (CA) was established and subjected to LITUS. Neurological function was assessed through behavioral tests and neurofunctional scoring. Hematoxylin and Eosin (HE) staining was employed to evaluate brain injury, while proteomic analysis was utilized to identify potential target proteins and pathways. Cells involved in pharmacological interventions or gene knockdown were subjected to oxygen/glucose deprivation/reoxygenation to mimic ischemia-reperfusion conditions in the brain. Protein-protein interactions were confirmed through co-immunoprecipitation. Intracellular calcium (Ca2+) influx was quantified using live-cell calcium imaging and flow cytometry. Cell viability was assessed using the Cell Counting Kit-8 (CCK8) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the expression of targeted genes. The expression of related proteins was detected through immunofluorescence and Western blotting assays. Results LITUS administration significantly improves 24-hour survival rates, promotes neurological function recovery, attenuates brain injury, and activates neurons in mice subjected to CPR. In vitro experiments revealed that ultrasound (US) mediates Ca2+ influx via the synergistic action of Piezo1 and Dkk3, thereby suppressing inflammatory responses, augmenting cell vitality, and promoting neuronal activation. These findings strongly indicate that the neuroprotective effects of LITUS may be mediated via the Piezo1-Dkk3/Ca2+/PI3K-Akt3 pathway. Conclusions This study firstly elucidates the neuroprotective effects of LITUS on PCABI and clarifies the potential mechanism. We posit that this study broadens the evidence base supporting future research into the application of LITUS in clinical PCABI patients.

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Section: Discussionmentioning

confidence: 99%

Low-intensity transcranial ultrasound (LITUS) exerts neuroprotective effects by modulating inflammatory responses via the Piezo1-Dkk3/Ca 2+ /PI3K-Akt signaling pathway

Xu,

Gu,

Liu

et al. 2024

Preprint

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“…Non-invasive brain stimulation has shown positive results in studies treating MDD by enhancing cortical plasticity [53,54]. Excitingly, TUS has been shown to enhance synaptic plasticity in rodents and even humans [55][56][57]. Though some studies have shown that TUS induced changes in neural responses that were transient, Niu et al's study showed that TUS could induce long-term changes in synaptic plasticity in rat hippocampus [56].…”

Section: Discussionmentioning

confidence: 99%

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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“…At the cellular or synaptic level, LIPUS stimulation can significantly increase the density of dendritic spines and enhance synaptic plasticity [ 24 , 25 ]. Furthermore, over a course of 2 years targeting at caudate and putamen in a Macaca mulatta primate model, LIPUS enhanced the resting state functional connectivity to the superior temporal cortex and insular cortex [ 26 ].…”

Section: Ow-intensity Focused Ultrasoundmentioning

confidence: 99%

Application of transcranial brain stimulation in dementia

Luo

Yang

2023

Tzu Chi Medical Journal

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The number of patients with dementia grows rapidly as the global population ages, which posits tremendous health-care burden to the society. Only cholinesterase inhibitors and a N-methyl-D-aspartate receptor antagonist have been approved for treating patients with Alzheimer’s disease (AD), and their clinical effects remained limited. Medical devices serve as an alternative therapeutic approach to modulating neural activities and enhancing cognitive function. Four major brain stimulation technologies including deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and transcranial ultrasound stimulation (TUS) have been applied to AD in a clinical trial setting. DBS allows electrical stimulation at the specified nucleus but remains resource-demanding, and after all, an invasive surgery; whereas TMS and tDCS are widely available and affordable but less ideal with respect to localization. The unique physical property of TUS, on the other hand, allows both thermal and mechanical energy to be transduced and focused for neuromodulation. In the context of dementia, using focused ultrasound to induce blood-brain barrier opening for delivering drugs and metabolizing amyloid protein has drawn great attention in recent years. Furthermore, low-intensity pulsed ultrasound has demonstrated its neuroprotective effects in both in vitro and in vivo studies, leading to ongoing clinical trials for AD. The potential and limitation of transcranial brain stimulation for treating patients with dementia would be discussed in this review.

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Modulation effects of low-intensity transcranial ultrasound stimulation on the neuronal firing activity and synaptic plasticity of mice

Cited by 12 publications

References 58 publications

Low-intensity transcranial ultrasound (LITUS) exerts neuroprotective effects by modulating inflammatory responses via the Piezo1-Dkk3/Ca 2+ /PI3K-Akt signaling pathway

Low-intensity transcranial ultrasound (LITUS) exerts neuroprotective effects by modulating inflammatory responses via the Piezo1-Dkk3/Ca 2+ /PI3K-Akt signaling pathway

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

Application of transcranial brain stimulation in dementia

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