Transcranial ultrasound stimulation relieves depression in mice with chronic restraint stress
Yiyue Zhu, Jiaru He, Canwen Wu, Jim‐Wei Wu, Zhongwen Cheng, Yan Chen, Maodan Yuan, Lvming Zeng, Xuanrong Ji
Abstract
Abstract Objective. Exhaustion of Serotonin (5-hydroxytryptamine, 5-HT) is a typical cause of the depression disorder’s development and progression, including depression-like behaviors. Transcranial ultrasound stimulation (TUS) is an emerging non-invasive neuromodulation technique treating various neurodegenerative diseases. This study aims to investigate whether TUS ameliorates depression-like behaviors by restoring 5-HT levels. Methods. The depression model mice are established by chronic restraint stress (CRS). Ultrasound waves (FF = 1.1 MHz, PRF = 1000 Hz, TBD = 0.5 ms, SD = 1 s, ISI = 1 s, and DC = 50%) were delivered into the dorsal raphe nucleus (DRN) for 30 min per day for 2 weeks. Depression-like behavior changes are evaluated with the sucrose preference and tail suspension tests. Liquid chromatography–mass spectrometry is performed to quantitatively detect the concentration of 5-HT in the DRN to explore its potential mechanism. The effectiveness and safety of TUS were assessed by c-Fos immunofluorescence and hematoxylin and eosin (HE) staining, respectively. Results. Three weeks after CRS, 22 depressive mice models were screened by sucrose preference index (SPI). After 2 weeks of ultrasound stimulation of the DRN (DRN-TUS) in depressive mice, the SPI was increased ( p = 0.1527) and the tail suspension immobility duration was significantly decreased ( p = 0.0038) compared with the non-stimulated group. In addition, TUS significantly enhances the c-Fos ( p = 0.05) positive cells’ expression and the 5-HT level ( p = 0.0079) in the DRN. Importantly, HE staining shows no brain tissue damage. Conclusion. These results indicate that DRN-TUS has safely and effectively improved depression-like behaviors including anhedonia and hopelessness, potentially by reversing the depletion of 5-TH. Significance TUS may provide a new perspective on depression therapy, possibly through restoring monoamine levels.