Dexmedetomidine Pretreatment Improves Lipopolysaccharide-induced Iron Homeostasis Disorder in Aged Mice

Background: Iron homeostasis disorder and neuroinflammation are the most commonly known factors that promote the occurrence and development of cognitive impairment in people. Dexmedetomidine has an anti-inflammatory effect, and it reduces the incidence of postoperative cognitive dysfunction. Therefore, the aim of this study is to verify whether dexmedetomidine could improve lipopolysaccharide-induced iron homeostasis disorder in aged mice, and show neuroprotective effect. Methods: First part, forty 12 month old male Kunming(KM) mice were divided into group N and group D: Normal saline group (group N), Dexmedetomidine group (group D). Second part, sixty 12-month-old male KM mice were divided into the following three groups: Normal saline group (group N), Lipopolysaccharide group (group LPS) and Dexmedetomidine Lipopolysaccharide group (group D + LPS). The mice in group D + LPS were given dexmedetomidine, and given LPS intraperitoneally 2 h later. Mice underwent an oriented navigation test and a space exploration test in the Morris Water maze (MWM) test. The expression levels of Interleukin-6 ( IL-6), L-ferritin (FTL) and Transferrin receptor-1 (TfR1) in hippocampus were detected by the Western blot analysis; the hippocampal hepcidin mRNA was detected by Real-time PCR(RT-PCR); the reactive oxygen species (ROS) in the hippocampus was measured using ROS test kit. Results: Dexmedetomidine improved the cognitive decline induced by LPS. Dexmedetomidine reduced the level of hippocampal IL-6, and it attenuated the increase in their levels caused by LPS. It had no effect on hippocampal hepcidin mRNA, FTL, TfR1 and ROS but it could attenuate the increase caused by LPS. Conclusion: Dexmedetomidine has no effect on iron metabolism pathway, but it can improve the cognitive decline and the iron disorder by reducing neuroinflammation and oxidative stress. The research indicates that dexmedetomidine plays a neuroprotective role.