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Abstract: The team of Professor Lei Sun from the Department of Biomedical Engineering of the Hong Kong Polytechnic University used low-frequency and low-intensity ultrasound to drive biogenic nanogas vesicles to achieve precise, reversible and reproducible neuromodulation in the deep brain region of mice
.
Keywords: low-frequency low-intensity ultrasound, nano gas vesicles, transcranial ultrasound neuromodulation Transcranial ultrasound neuromodulation (Transcranial ultrasound stimulation, TUS) is a promising new generation of neuromodulation technology
.
Transcranial ultrasound can pass through the skull non-destructively and be focused on the millimeter-level deep brain region.
It has shown great potential in human brain function research and disease treatment
.
How to achieve precise ultrasound neuromodulation is an important research direction at present
.
Methods currently under development include: ultrasound acoustic genetics, ultrasound thermal genetics, and so on
.
This article provides a new way to go in parallel with it
.
"Gas vesicles (GVs)" is a unique gene-encoded gas-rich protein nanostructure, which is mainly expressed in aquatic photosynthetic organisms as a means of regulating buoyancy
.
It has unique acoustic properties.
In recent years, a series of studies have shown its great potential in ultrasound molecular imaging, and it is considered to be the "fluorescent protein" in ultrasound imaging
.
GVs can be targeted and expressed in specific locations or cells through minimally invasive delivery (microinjection or ultrasound blood-brain barrier opening) and gene editing technology under development
.
GVs will vibrate in the sound field.
Researchers try to use this phenomenon to concentrate ultrasound energy near GVs, so that a lower ultrasound intensity can be used to achieve targeted regulation of deep brain regions
.
The results of the study show that GVs may not only be the "fluorescent protein" in ultrasound, but also the "ChR2" in ultrasound other than the mechanically sensitive ion channel protein, which is expected to mediate ultrasound imaging and stimulation at the same time
.
Figure 1.
Experimental schematic diagram
.
GV vibrates under an ultrasonic field, triggering the opening of mechanically sensitive ion channels on the surface of neurons, and calcium ion influx, activating neurons in the deep brain area of mice
.
This study first started with isolated primary neuronal cells and used calcium imaging as a research tool to prove that GV+US triggers calcium influx and neuronal activation (Figure 2a)
.
Adding a mechanosensitive ion channel blocker (RR) can reduce the calcium response, indicating that GV+US triggers the opening of the mechanosensitive ion channel and mediates the influx of calcium ions (Figure 2b)
.
In addition, the results of in vivo studies in mice show that GV+US can precisely regulate neurons in deep brain regions, displaying reversible and repeatable calcium responses, and the corresponding changes in neuronal calcium signals can be recorded by Fiber Photometry (FP).
The control group There is no similar reaction (Figure 2c)
.
The recorded calcium signal response is within 250 ms of the ultrasound transmission delay time, showing that the stimulation method has a high time resolution (Figure 2d)
.
The researchers tested the neuron activation marker c-Fos.
When GV was injected into the Ventral Tegmental Area (VTA) in the deep brain area of mice, the expression of c-Fos was mainly concentrated in the VTA area, while the control group showed little c-Fos Expression (Figure 2e & f), which indicates that GV+US can successfully activate neurons in deep brain regions and has spatial targeting
.
Figure 2.
GV mediates US activation of neurons
.
a) GV+US triggers neuronal calcium influx; b) RR inhibits neuronal calcium influx; c) FP records the calcium ion response of VTA neurons (light blue rectangular bars indicate ultrasound pulses); d) ultrasound stimulation to calcium response E) Mouse whole brain c-Fos expression map; f) C-Fos statistical results map in the 200 × 200 µm VTA area of the brain slice
.
Based on the above conclusions, the researchers demonstrated a biogenic nanobubble-mediated ultrasound precision neuromodulation technology, which lays a solid foundation for the basic research and clinical application of deep brain neuromodulation in the future
.
Professor Lei Sun from the Department of Biomedical Engineering of the Hong Kong Polytechnic University is the corresponding author of the paper.
PhD students Hou Xuandi, Dr.
Qiu Zhihai, and Dr.
Xian Quanxiang are the co-first authors of the paper
.
WILEY paper information: Precise Ultrasound Neuromodulation in a Deep Brain Region Using Nano Gas Vesicles as ActuatorsXuandi Hou, Zhihai Qiu, Quanxiang Xian, Shashwati Kala, Jianing Jing, Kin Fung Wong, Jiejun Zhu, Jinghui Guo, Ting Zhu, Minyi Yang, Lei SunAdvanced ScienceDOI: 10.
1002/advs.
202101934 Click "Read the original text" in the lower left corner to view the original text of the paper
.
Introduction to AdvancedScience Journal "Advanced Science" (Advanced Science) Wiley's high-quality open source journal founded in 2014, publishes innovative achievements and cutting-edge progress in materials science, physical chemistry, biomedicine, engineering and other fields
.
The journal is dedicated to disseminating scientific research results to the public to the greatest extent, and all articles are freely available
.
The latest impact factor is 16.
806, and the 2020 SCI journals of the Chinese Academy of Sciences will be divided into the Q1 area of the material science category and the Q1 area of the engineering technology category
.
Press and hold the QR code on the official WeChat platform of AdvancedScienceNewsWiley's scientific research information.
Follow us to share cutting-edge information｜Focus on scientific research trends to publish scientific research news or apply for information sharing, please contact: ASNChina@Wiley.
com
.
Keywords: low-frequency low-intensity ultrasound, nano gas vesicles, transcranial ultrasound neuromodulation Transcranial ultrasound neuromodulation (Transcranial ultrasound stimulation, TUS) is a promising new generation of neuromodulation technology
.
Transcranial ultrasound can pass through the skull non-destructively and be focused on the millimeter-level deep brain region.
It has shown great potential in human brain function research and disease treatment
.
How to achieve precise ultrasound neuromodulation is an important research direction at present
.
Methods currently under development include: ultrasound acoustic genetics, ultrasound thermal genetics, and so on
.
This article provides a new way to go in parallel with it
.
"Gas vesicles (GVs)" is a unique gene-encoded gas-rich protein nanostructure, which is mainly expressed in aquatic photosynthetic organisms as a means of regulating buoyancy
.
It has unique acoustic properties.
In recent years, a series of studies have shown its great potential in ultrasound molecular imaging, and it is considered to be the "fluorescent protein" in ultrasound imaging
.
GVs can be targeted and expressed in specific locations or cells through minimally invasive delivery (microinjection or ultrasound blood-brain barrier opening) and gene editing technology under development
.
GVs will vibrate in the sound field.
Researchers try to use this phenomenon to concentrate ultrasound energy near GVs, so that a lower ultrasound intensity can be used to achieve targeted regulation of deep brain regions
.
The results of the study show that GVs may not only be the "fluorescent protein" in ultrasound, but also the "ChR2" in ultrasound other than the mechanically sensitive ion channel protein, which is expected to mediate ultrasound imaging and stimulation at the same time
.
Figure 1.
Experimental schematic diagram
.
GV vibrates under an ultrasonic field, triggering the opening of mechanically sensitive ion channels on the surface of neurons, and calcium ion influx, activating neurons in the deep brain area of mice
.
This study first started with isolated primary neuronal cells and used calcium imaging as a research tool to prove that GV+US triggers calcium influx and neuronal activation (Figure 2a)
.
Adding a mechanosensitive ion channel blocker (RR) can reduce the calcium response, indicating that GV+US triggers the opening of the mechanosensitive ion channel and mediates the influx of calcium ions (Figure 2b)
.
In addition, the results of in vivo studies in mice show that GV+US can precisely regulate neurons in deep brain regions, displaying reversible and repeatable calcium responses, and the corresponding changes in neuronal calcium signals can be recorded by Fiber Photometry (FP).
The control group There is no similar reaction (Figure 2c)
.
The recorded calcium signal response is within 250 ms of the ultrasound transmission delay time, showing that the stimulation method has a high time resolution (Figure 2d)
.
The researchers tested the neuron activation marker c-Fos.
When GV was injected into the Ventral Tegmental Area (VTA) in the deep brain area of mice, the expression of c-Fos was mainly concentrated in the VTA area, while the control group showed little c-Fos Expression (Figure 2e & f), which indicates that GV+US can successfully activate neurons in deep brain regions and has spatial targeting
.
Figure 2.
GV mediates US activation of neurons
.
a) GV+US triggers neuronal calcium influx; b) RR inhibits neuronal calcium influx; c) FP records the calcium ion response of VTA neurons (light blue rectangular bars indicate ultrasound pulses); d) ultrasound stimulation to calcium response E) Mouse whole brain c-Fos expression map; f) C-Fos statistical results map in the 200 × 200 µm VTA area of the brain slice
.
Based on the above conclusions, the researchers demonstrated a biogenic nanobubble-mediated ultrasound precision neuromodulation technology, which lays a solid foundation for the basic research and clinical application of deep brain neuromodulation in the future
.
Professor Lei Sun from the Department of Biomedical Engineering of the Hong Kong Polytechnic University is the corresponding author of the paper.
PhD students Hou Xuandi, Dr.
Qiu Zhihai, and Dr.
Xian Quanxiang are the co-first authors of the paper
.
WILEY paper information: Precise Ultrasound Neuromodulation in a Deep Brain Region Using Nano Gas Vesicles as ActuatorsXuandi Hou, Zhihai Qiu, Quanxiang Xian, Shashwati Kala, Jianing Jing, Kin Fung Wong, Jiejun Zhu, Jinghui Guo, Ting Zhu, Minyi Yang, Lei SunAdvanced ScienceDOI: 10.
1002/advs.
202101934 Click "Read the original text" in the lower left corner to view the original text of the paper
.
Introduction to AdvancedScience Journal "Advanced Science" (Advanced Science) Wiley's high-quality open source journal founded in 2014, publishes innovative achievements and cutting-edge progress in materials science, physical chemistry, biomedicine, engineering and other fields
.
The journal is dedicated to disseminating scientific research results to the public to the greatest extent, and all articles are freely available
.
The latest impact factor is 16.
806, and the 2020 SCI journals of the Chinese Academy of Sciences will be divided into the Q1 area of the material science category and the Q1 area of the engineering technology category
.
Press and hold the QR code on the official WeChat platform of AdvancedScienceNewsWiley's scientific research information.
Follow us to share cutting-edge information｜Focus on scientific research trends to publish scientific research news or apply for information sharing, please contact: ASNChina@Wiley.
com
