Deoxycholic acid mediates neuroinflammatory responses under hypoxia exposure
10.7644/j.issn.1674-9960.2025.05.002
- VernacularTitle:脱氧胆酸介导低氧应激诱发神经炎症反应的作用机制研究
- Author:
Haoran CUI
1
;
Chen XING
;
Lun SONG
Author Information
1. 军事科学院军事医学研究院,北京 100850
- Keywords:
hypoxia at high altitude;
gut-brain axis;
tauroursodeoxycholic acid;
neuroinflammation
- From:
Military Medical Sciences
2025;49(5):330-336
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the roles and mechanism of deoxycholic acid(DCA)in mediating the neuroinflammatory responses induced by hypobaric hypoxia.Methods C57BL/6J mice were randomly divided into thecontrol group(Con),tauroursodeoxycholic acid(TUDCA)group,hypoxia group(Hyp)and hypoxia+TUDCA group(Hyp+TUDCA).The mice were exposed in a hypoxic chamber for 48 h,which could mimic the high altitude environment.The levels of total bile acids(BA),lithocholic acid(LCA)and deoxycholic acid(DCA)in the serum and colon of mice were detected using enzyme-linked immunosorbent assay(ELISA),so were levels of DCA in the cortex,hippocampus and hypothalamus.The role of DCA in inducing neuroinflammation and IL-1β and TNF-α expressions was evaluated by knocking down the DCA receptor,farnesoid X receptor(FXR)in the N9 microglial cells and by administrating TUDCA to mice followed by hypoxia exposure.Real-time quantitative PCR(qPCR)and immunofluorescence staining were used to detect the activation of microglia and expression levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in the cortex of mice in each group.Results Hypoxia exposure increased DCA levels in the colon,serum and cortex.Under the same conditions,cortical microglia were activated,along with the elevation of IL-1β and TNF-α levels.DCA treatment increased the expression levels of FXR,IL-1β and TNF-α in N9 microglial cells.Knocking down the expression level of FXR inhibited DCA-induced IL-1β and TNF-α expressions in N9 cells.Furthermore,administration of TUDCA inhibited microglial activation and elevation of IL-1β in the cortex induced by hypoxia.Conclusion DCA can serve as a mediator in neuroinflammation by activating FXR in the cortex under hypoxia exposure.TUDCA administration can be used to mitigate neuroinflammation induced by hypoxia.
