Chengchao Zuo1, Huan Cao1, Fang Feng2, Guo Li1, Yaqi Huang1, Liudi Zhu1, Zhongya Gu1, Yuyan Yang1, Jianguo Chen3, Yongsheng Jiang4, Furong Wang5. 1. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan 430030, Hubei, China. 2. Department of Neurology, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, China. 3. Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; The Research Center for Depression, Tongji Medical College, Huazhong University of Science, Wuhan, Hubei, China; Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, Hubei, China; Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China. 4. Cancer Center of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan 430030, Hubei, China. Electronic address: ysjiang.china@163.com. 5. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Road, Wuhan 430030, Hubei, China. Electronic address: wangfurong.china@163.com.
Abstract
AIMS: Recently numerous studies have demonstrated that neuroinflammation plays a critical role in the pathogenesis of depression. Repetitive transcranial magnetic stimulation (rTMS) has been used to treat depression for years but its mechanism is not fully elucidated. The present study was designed to investigate whether rTMS could alleviate neuroglia-associated neuro-inflammatory process in mice models of depression. METHODS: Mice were treated with chronic unpredictable mild stress (CUMS) to induce depression models and received four weeks of 15 Hz rTMS. Then the depression-like behaviors, microglia activation, the level of astrocytes, pro-inflammatory cytokines and inflammation-related signaling pathways were evaluated. RESULTS: rTMS ameliorated depression-like behaviors in CUMS-treated mice. rTMS not only markedly alleviated the activation of microglia but induced a switch of microglia polarization from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype in the hippocampus and prefrontal cortex. Meanwhile, rTMS reversed the down-regulation of astrocytes and inhibited high levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-alpha (TNF-α) caused by CUMS in above regions. Moreover, we found that anti-inflammatory actions by rTMS were associated with the TLR4/NF-κB/NLRP3 signaling pathway. CONCLUSION: Collectively, our findings indicate that rTMS can exert anti-inflammatory actions in depression and provide new insights into the mechanism of rTMS in the treatment of depression.
AIMS: Recently numerous studies have demonstrated that neuroinflammation plays a critical role in the pathogenesis of depression. Repetitive transcranial magnetic stimulation (rTMS) has been used to treat depression for years but its mechanism is not fully elucidated. The present study was designed to investigate whether rTMS could alleviate neuroglia-associated neuro-inflammatory process in mice models of depression. METHODS: Mice were treated with chronic unpredictable mild stress (CUMS) to induce depression models and received four weeks of 15 Hz rTMS. Then the depression-like behaviors, microglia activation, the level of astrocytes, pro-inflammatory cytokines and inflammation-related signaling pathways were evaluated. RESULTS: rTMS ameliorated depression-like behaviors in CUMS-treated mice. rTMS not only markedly alleviated the activation of microglia but induced a switch of microglia polarization from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype in the hippocampus and prefrontal cortex. Meanwhile, rTMS reversed the down-regulation of astrocytes and inhibited high levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-alpha (TNF-α) caused by CUMS in above regions. Moreover, we found that anti-inflammatory actions by rTMS were associated with the TLR4/NF-κB/NLRP3 signaling pathway. CONCLUSION: Collectively, our findings indicate that rTMS can exert anti-inflammatory actions in depression and provide new insights into the mechanism of rTMS in the treatment of depression.