Human umbilical cord mesenchymal stem cells ameliorate depression by regulating Jmjd3 and microglia polarization in myocardial infarction mice

Psychopharmacology (Berl). 2021 Oct;238(10):2973-2984. doi: 10.1007/s00213-021-05912-w. Epub 2021 Aug 10.

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.

Keywords: Depression; HUC-MSCs; Inflammation; Jmjd3; Microglia; Myocardial infarction.

MeSH terms

  • Animals
  • Depression
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells*
  • Mice
  • Microglia
  • Myocardial Infarction* / therapy
  • Umbilical Cord