Jinniu Zhang1, Hui Zhou2, Jian Yang1,3, Jun Jia4, Lili Niu2, Zuoli Sun1, Dandan Shi1, Long Meng2, Weibao Qiu2, Xiaomin Wang4, Hairong Zheng2, Gang Wang1,3. 1. The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China. 2. Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. 3. Key Laboratory for the Neurodegenerative Disorders of the Chinese Ministry of Education, Department of Physiology, Capital Medical University, Beijing, China. 4. Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
Abstract
INTRODUCTION: There is an unmet need for better nonpharmaceutical treatments for depression. Low-intensity pulsed ultrasound (LIPUS) is a novel type of neuromodulation that could be helpful for depressed patients. OBJECTIVE: The goal of this study was to investigate the feasibility and potential mechanisms of LIPUS in the treatment of depression. METHODS: Chronic unpredictable stress (CUS) was used to generate rats with depression-like features that were treated with four weeks of LIPUS stimulation of the ventromedial prefrontal cortex. Depression-like behaviors were assessed with the sucrose preference, forced swim, and open field tests. BDNF/mTORC1 signaling was examined by Western blot to investigate this potential molecular mechanism. The safety of LIPUS was evaluated using hematoxylin-eosin and Nissl staining. RESULTS: Four weeks of LIPUS stimulation significantly increased sucrose preference and reduced forced swim immobility time in CUS rats. LIPUS also partially reversed the molecular effects of CUS that included decreased levels of BDNF, phosphorylated tyrosine receptor kinase B (TrkB), extracellular signal-regulated kinase (ERK), mammalian target of rapamycin complex 1 (mTORC1), and S6 kinase (S6K). Moreover, histological staining revealed no gross tissue damage. CONCLUSIONS: Chronic LIPUS stimulation can effectively and safely improve depression-like behaviors in CUS rats. The underlying mechanisms may be related to enhancement of BDNF/ERK/mTORC1 signaling pathways in the prefrontal cortex (PFC). LIPUS is a promising noninvasive neuromodulation tool that merits further study as a potential treatment for depression.
INTRODUCTION: There is an unmet need for better nonpharmaceutical treatments for depression. Low-intensity pulsed ultrasound (LIPUS) is a novel type of neuromodulation that could be helpful for depressed patients. OBJECTIVE: The goal of this study was to investigate the feasibility and potential mechanisms of LIPUS in the treatment of depression. METHODS: Chronic unpredictable stress (CUS) was used to generate rats with depression-like features that were treated with four weeks of LIPUS stimulation of the ventromedial prefrontal cortex. Depression-like behaviors were assessed with the sucrose preference, forced swim, and open field tests. BDNF/mTORC1 signaling was examined by Western blot to investigate this potential molecular mechanism. The safety of LIPUS was evaluated using hematoxylin-eosin and Nissl staining. RESULTS: Four weeks of LIPUS stimulation significantly increased sucrose preference and reduced forced swim immobility time in CUS rats. LIPUS also partially reversed the molecular effects of CUS that included decreased levels of BDNF, phosphorylated tyrosine receptor kinase B (TrkB), extracellular signal-regulated kinase (ERK), mammalian target of rapamycin complex 1 (mTORC1), and S6 kinase (S6K). Moreover, histological staining revealed no gross tissue damage. CONCLUSIONS: Chronic LIPUS stimulation can effectively and safely improve depression-like behaviors in CUS rats. The underlying mechanisms may be related to enhancement of BDNF/ERK/mTORC1 signaling pathways in the prefrontal cortex (PFC). LIPUS is a promising noninvasive neuromodulation tool that merits further study as a potential treatment for depression.
Authors: Paul E Holtzheimer; Mary E Kelley; Robert E Gross; Megan M Filkowski; Steven J Garlow; Andrea Barrocas; Dylan Wint; Margaret C Craighead; Julie Kozarsky; Ronald Chismar; Jared L Moreines; Klaus Mewes; Patricio Riva Posse; David A Gutman; Helen S Mayberg Journal: Arch Gen Psychiatry Date: 2012-01-02
Authors: Kullervo Hynynen; Gregory T Clement; Nathan McDannold; Natalia Vykhodtseva; Randy King; P Jason White; Shuki Vitek; Ferenc A Jolesz Journal: Magn Reson Med Date: 2004-07 Impact factor: 4.668
Authors: Mi Kyoung Seo; Cheol Min Choi; Roger S McIntyre; Hye Yeon Cho; Chan Hong Lee; Rodrigo B Mansur; Yena Lee; Jae-Hon Lee; Young Hoon Kim; Sung Woo Park; Jung Goo Lee Journal: BMC Neurosci Date: 2017-04-26 Impact factor: 3.288