ArticleNeuropsychiatric disease and treatment2026
Parameter-Specific Effects of Low-Intensity Transcranial Focused Ultrasound Stimulation on Depression-Like Behaviors in a CUMS Mouse Model.
Article in Neuropsychiatric disease and treatment, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: Depression is a multifactorial disorder involving neurotransmitter dysregulation, gut microbiota imbalance, and metabolic disturbances. Low-intensity transcranial focused ultrasound stimulation (LIFUS) holds promise for treating depression. However, the effects of different LIFUS parameter settings on depression-like behaviors, and their potential associations with gut microbiota and fecal metabolite changes, remain largely unexplored. This study aims to investigate the parameter-specific effects of LIFUS on depression-like behaviors in a chronic unpredictable mild stress (CUMS) mouse model, and to explore potential associations with changes in gut microbiota and fecal metabolites. Methods: To establish a depression model, C57BL/6 mice were subjected to CUMS, while a separate cohort was kept as a control (CON) group. The CUMS-exposed mice were then randomly divided into four groups: CUMSpo, LIFUS1, LIFUS2 and SHAM. Depressive-like behaviors were evaluated using the sucrose preference test (SPT) and forced swim test (FST). The levels of neurotransmitters and Fecal concentrations of metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gut microbiota composition was analyzed by metagenomic sequencing, and α-diversity was assessed using the ACE, Chao1, and Shannon indices. Histopathology was assessed via HE staining. Results: LIFUS at 1.5 kHz PRF, but not 300 Hz, significantly attenuated CUMS-induced depressive-like behaviors, evidenced by increased sucrose preference and reduced immobility time, without affecting locomotor activity. This behavioral effect was accompanied by a significant increase in cortical glutamate. LIFUS2 protocol was associated with a significant increase in tryptamine, alongside a concurrent trend towards restoring the abundance of Clostridia and enhancing gut microbiota α-diversity. HE staining confirmed protocol safety. Conclusion: The antidepressant-like effects of LIFUS appear to be associated with multi-systemic alterations, including changes in cortical glutamate, modulation of the gut microbiota, and specific changes in tryptophan metabolism.
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