To investigate the roles and mechanism of deoxycholic acid (DCA) in mediating the neuroinflammatory responses induced by hypobaric hypoxia.

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.

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.

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.