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Parameter-Specific Effects of Low-Intensity Transcranial Focused Ultrasound Stimulation on Depression-Like Behaviors
Yan Zhang1,2,3, Yaxing Zhang1,2,3, Kaiming Zhang1,2,3
1Department of Psychiatry, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050031, People's Republic of China.
Low-intensity focused ultrasound (LIFUS) at 1.5 kHz improved depression-like behaviors in mice by altering brain glutamate and gut metabolites. This novel approach shows promise for depression treatment by influencing gut microbiota and tryptophan metabolism.
Area of Science:
- Neuroscience
- Microbiology
- Metabolomics
Background:
- Depression is a complex disorder linked to neurotransmitter imbalance, gut microbiota dysregulation, and metabolic issues.
- Low-intensity focused ultrasound stimulation (LIFUS) is a potential therapeutic for depression, but optimal parameters and mechanisms are unclear.
- Understanding LIFUS effects on behavior, gut microbiota, and metabolites is crucial for developing effective depression treatments.
Purpose of the Study:
- To investigate the impact of different LIFUS parameter settings on depression-like behaviors in a mouse model.
- To explore the relationship between LIFUS treatment, gut microbiota composition, and fecal metabolite profiles.
- To identify specific LIFUS parameters that effectively alleviate depression-like behaviors.
Main Methods:
- A chronic unpredictable mild stress (CUMS) mouse model was used to induce depression-like behaviors.
- Mice were treated with different LIFUS parameters (1.5 kHz vs. 300 Hz) or sham stimulation.
- Behavioral tests (sucrose preference, forced swim), neurotransmitter analysis, fecal metabolite profiling (LC-MS/MS), and gut microbiota sequencing were performed.
Main Results:
- LIFUS at 1.5 kHz significantly reduced depression-like behaviors and increased cortical glutamate levels.
- The 1.5 kHz LIFUS protocol also led to increased tryptamine, a trend towards restoring Clostridia abundance, and enhanced gut microbiota diversity.
- No significant effects on locomotor activity were observed, and histopathology confirmed safety.
Conclusions:
- LIFUS, particularly at 1.5 kHz, demonstrates antidepressant-like effects in a mouse model.
- These effects are associated with multi-systemic changes, including increased cortical glutamate, altered gut microbiota, and specific modifications in tryptophan metabolism.
- LIFUS represents a promising non-invasive neuromodulation technique for depression treatment.
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