Dexmedetomidine alleviates LPS-induced neuronal dysfunction via AKT/GSK-3β/CRMP-2 pathway

Background: Dexmedetomidine (Dex), an α2-adrenergic receptor agonist, shows intervention effect on cognitive dysfunction in elderly patients after general anesthesia. However, the underlying pathological mechanism remains to be further elucidated. The aim of the study was to investigate effects of Dex on LPS-induced neuronal damages in cultured hippocampal neurons. Methods We applied LPS to mimic the post-surgical inflammation in cultured hippocampal neuron. Cultured hippocampal neurons were treated with LPS in a dose- and time- dependent manner, then were administrated with or without Dex. The neuronal morphology including neurite outgrowth and synaptic transmission was observed, and mEPSCs was recorded by electrophysiological patch clamp. Cell lysates were subjected for western blot to assess the explore the potential underlying mechanism. Results Compared to control group, administration of LPS significantly impaired the neurite outgrowth in a concentration- and time-dependent manner. Dex treatment markedly reversed LPS-induced impairment of neurite outgrowth in hippocampal neurons. Electrophysiological patch clamp results showed that LPS induced synaptic transmission dysfunction, which could be restored after Dex addition. Furthermore, western blotting assays showed that LPS suppressed the AKT/GSK-3β/CRMP-2 signaling pathway and Dex administration significantly re-activated this pathway to encounter the inhibitory effect of LPS. Conclusion Addition of Dex showed significant protection effect on LPS-induced hippocampal neuron damages, including neurite outgrowth and synaptic transmission. Dex functioned via the activation of GSK-3β/CRMP-2 signaling pathway to alleviate LPS-induced neurological dysfunctions.