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Nitric Oxide-Mediated Minimally Invasive Neuromodulation through Gut-Brain Axis via a Bioelectronic Microdevice for
Qinjuan Ren1, Zhiqiang Chang1, Ya Zhang2,3
1Neurology and Neurological Rehabilitation Center, Shanghai Yangzhi Rehabilitation Hospital affiliated to Tongji University School of Medicine; The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, China.
ACS Nano
|June 29, 2026
Summary
A novel wireless device releases nitric oxide (NO) to non-invasively modulate brain function via the vagus nerve, alleviating depressive behaviors and restoring brain chemistry.
Area of Science:
- Neuroscience
- Bioelectronic Medicine
- Gastroenterology
Background:
- Minimally invasive brain modulation is crucial for neurological disorder research and treatment.
- Current methods often require direct brain intervention, posing risks and limitations.
- Developing non-invasive strategies for central nervous system regulation is a key therapeutic goal.
Purpose of the Study:
- To introduce a wireless, optically controlled nitric oxide (NO)-releasing microbioelectronic device (ONMD) for peripheral-to-central neuromodulation.
- To investigate the ONMD's mechanism of action involving NO-TRP signaling and vagus nerve activation.
- To evaluate the ONMD's efficacy in alleviating depressive-like behaviors and restoring neurochemical balance in a mouse model.
Main Methods:
- Development and application of a wireless, optically activated ONMD.
- Activation of transient receptor potential (TRP) channels by released NO to form a signaling hub.
- Selective stimulation of the vagus nerve and nucleus tractus solitarius (NTS) via peripheral device operation.
- Assessment of behavioral changes, peripheral inflammation markers, and central serotonin (5-HT) levels in mice.
Main Results:
- The ONMD successfully achieved peripheral-to-central neuromodulation without direct brain intervention.
- Light-activated NO release from the ONMD selectively stimulated the vagus nerve and NTS.
- ONMD treatment significantly alleviated depressive-like behaviors in mice.
- Therapeutic effects included reduced peripheral inflammation and restored central 5-HT homeostasis.
Conclusions:
- The ONMD offers a non-invasive, gasotransmitter-mediated strategy for regulating brain function.
- This peripheral bioelectronic approach provides a novel pathway for advancing neuropsychiatric therapies.
- The study demonstrates the potential of remote modulation of central circuits through peripheral activation.
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