Youyang Zhang1,2, Xinan Wang3, Yuhang Li2, Ruiping Liu2, Jiangqi Pan4, Xiane Tang5, Shuifen Sun6, Jie Liu6, Wenlin Ma7,8. 1. Department of Cardiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. 2. Department of Geriatrics, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. 3. Department of Urology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Rd, Putuo District, Shanghai, 200092, China. 4. Department of Cardiology, Gongli Hospital, Navy Military Medical University, Shanghai, China. 5. Department of Clinical Medicine, School of Medicine, Hubei University for Nationalities, Enshi, China. 6. Regenerative Medicine Research Center, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China. 7. Department of Cardiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. mawenlin@tongji.edu.cn. 8. Department of Geriatrics, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. mawenlin@tongji.edu.cn.
Abstract
RATIONALE: Microglia regulate the inflammation of the central nervous system and play a crucial role in the pathogenesis of depression. Moreover, Jmjd3 is involved in microglia polarization. Mounting studies reported the beneficial effects of human umbilical cord mesenchymal stem cells (HUC-MSCs) on myocardial infarction (MI), Unfortunately, its effects on MI-induced depression and its underlying mechanisms remain unclear. OBJECTIVES: We aimed to investigate the antidepressant effects of HUC-MSCs and their impacts on microglia polarization. METHODS: In the current study, the MI model was established by ligating the left anterior descending coronary artery. Mice were injected with HUC-MSCs or PBS through the tail vein 1week after the surgery. The sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST) were performed to evaluate depression-like behavior. Cardiac function and myocardial fibrosis were evaluated at the end of the experiments. Immunofluorescence, Western blot, ELISA, and qRT-PCR were used to detect the levels of Jmjd3 and microglia-related markers and inflammatory factors. RESULTS: HUC-MSC treatment significantly improved cardiac function, reduced the area of myocardial fibrosis, and alleviated depression-like behaviors induced by MI. HUC-MSCs inhibited the expression of Jmjd3 and promoted the switch of microglia in the prefrontal cortex, hypothalamus, and hippocampus from M1 to M2, thereby decreased the level of pro-inflammatory factors. CONCLUSION: HUC-MSCs have cardioprotective and potential anti-depressive effects induced by MI related to the inflammation improved by regulating Jmjd3 and microglial polarization.
RATIONALE: Microglia regulate the inflammation of the central nervous system and play a crucial role in the pathogenesis of depression. Moreover, Jmjd3 is involved in microglia polarization. Mounting studies reported the beneficial effects of human umbilical cord mesenchymal stem cells (HUC-MSCs) on myocardial infarction (MI), Unfortunately, its effects on MI-induced depression and its underlying mechanisms remain unclear. OBJECTIVES: We aimed to investigate the antidepressant effects of HUC-MSCs and their impacts on microglia polarization. METHODS: In the current study, the MI model was established by ligating the left anterior descending coronary artery. Mice were injected with HUC-MSCs or PBS through the tail vein 1week after the surgery. The sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST) were performed to evaluate depression-like behavior. Cardiac function and myocardial fibrosis were evaluated at the end of the experiments. Immunofluorescence, Western blot, ELISA, and qRT-PCR were used to detect the levels of Jmjd3 and microglia-related markers and inflammatory factors. RESULTS: HUC-MSC treatment significantly improved cardiac function, reduced the area of myocardial fibrosis, and alleviated depression-like behaviors induced by MI. HUC-MSCs inhibited the expression of Jmjd3 and promoted the switch of microglia in the prefrontal cortex, hypothalamus, and hippocampus from M1 to M2, thereby decreased the level of pro-inflammatory factors. CONCLUSION: HUC-MSCs have cardioprotective and potential anti-depressive effects induced by MI related to the inflammation improved by regulating Jmjd3 and microglial polarization.
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