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.
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Funding
This study was supported by the National Key R&D Program of China (2018YFC1314700), Shanghai Municipal Health Commission Foundation of Shanghai (2019ZB0202, 2019SY026), Tongji Hospital of Tongji University (ITJ[ZD]1809), and National Natural Science Foundation of China (82060242).
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Zhang, Y., Wang, X., Li, Y. et al. Human umbilical cord mesenchymal stem cells ameliorate depression by regulating Jmjd3 and microglia polarization in myocardial infarction mice. Psychopharmacology 238, 2973–2984 (2021). https://doi.org/10.1007/s00213-021-05912-w
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DOI: https://doi.org/10.1007/s00213-021-05912-w