Pinocembrin ameliorates intermittent hypoxia-induced neuroinflammation through BNIP3-dependent mitophagy in a murine model of sleep apnea

• Main Authors: Lin-Jing Gong, Xin-Yuan Wang, Wen-Yu Gu, Xu Wu
• Format: Article
• Language: English
• Published: BMC 2020-11-01
• Series: Journal of Neuroinflammation
• Subjects: Pinocembrin; Neuroinflammation; Microglia; Obstructive sleep apnea (OSA); BNIP3; Mitophagy
• Online Access: http://link.springer.com/article/10.1186/s12974-020-02014-w

Abstract Background Intermittent hypoxia (IH) caused by obstructive sleep apnea (OSA) leads to neuroinflammation. Pinocembrin has been shown to have neuroprotective effects, while the therapeutic functions under IH condition are still unknown. Methods An OSA model was established by CIH exposure inside custom-made chambers. C57BL/6 mice were intraperitoneally injected with pinocembrin (40 mg/kg, i.p.) or vehicle (PBS containing 5% povidone; i.p.), and the changes of behavior on mice were detected by the Morris water maze test. Immunohistochemical staining, western blotting, immunofluorescence assays, and immunoprecipitation were used to investigate the association between NLRP3 inflammasome and BNIP3-dependent mitophagy. The mitochondrial morphology and mitophagosomes were detected under a transmission electron microscope. The detrimental effects of IH were tested by annexin V-FITC/PI staining, Mito SOX Red staining, and JC-1 mitochondrial membrane potential assay. Results In this study, our observations in vivo indicated that the administration of pinocembrin can restore spatial learning and memory ability and reduce neuronal apoptosis and hippocampal inflammation. Pinocembrin treatment significantly inhibited the formation of NLRP3 inflammasome and infiltration of microglia and enhanced BNIP3-mediated mitophagy in the hippocampus of IH mice. Additionally, our in vitro results show that pinocembrin protects microglial cells against IH-induced cytotoxicity by activating BNIP3-dependent mitophagy through the JNK-ERK signaling pathway. Conclusions In summary, our findings demonstrated that pinocembrin can act as a potential therapeutic strategy for IH-induced neuroinflammation.