4.5 Article

Dexmedetomidine Alleviates LPS-Induced Neuronal Dysfunction by Modulating the AKT/GSK-3β/CRMP-2 Pathway in Hippocampal Neurons

期刊

NEUROPSYCHIATRIC DISEASE AND TREATMENT
卷 17, 期 -, 页码 671-680

出版社

DOVE MEDICAL PRESS LTD
DOI: 10.2147/NDT.S297365

关键词

dexmedetomidine; postoperative cognitive dysfunction; neurological impairment; AKT; GSK-3; CRMP-2

资金

  1. Medical Scientific Research Foundation of Guangdong Province, China [B2021190]

向作者/读者索取更多资源

This study found that dexmedetomidine can reverse the hippocampal neuron damage caused by lipopolysaccharide, including neurite outgrowth and synaptic transmission dysfunction. By activating the AKT/GSK-3β/CRMP-2 signaling pathway, dexmedetomidine can alleviate LPS-induced neurological dysfunction.
Objective: Dexmedetomidine, an ?2-adrenergic receptor agonist, mitigates cognitive dysfunction in elderly patients after surgery with general anesthesia. However, the underlying mechanism by which dexmedetomidine reduces cognitive dysfunction remains to be fully elucidated. The aim of this study was to investigate the effects of dexmedetomidine on lipopolysaccharide (LPS)-induced neuronal dysfunction in cultured hippocampal neurons. Methods: LPS, in the presence and absence of dexmedetomidine, was applied to cultured hippocampal neurons to mimic post-surgical inflammation. Neuronal morphology, including neurite outgrowth and synaptic transmission, was observed, and miniature excitatory post synaptic currents were recorded by electrophysiological patch-clamp. Results: LPS significantly impaired neurite outgrowth in hippocampal neurons in a concentration-and time-dependent manner, which was reversed by dexmedetomidine treatment. Electrophysiological patch-clamp results showed that LPS induced synaptic transmission dysfunction, which was restored after dexmedetomidine addition. Furthermore, Western blotting assays showed that LPS suppressed the AKT/GSK-3?/CRMP-2 signaling pathway and dexmedetomidine countered the inhibitory effect of LPS by re-activating this pathway. Conclusion: In general, dexmedetomidine protected against the effects of LPS-induced hippocampal neuron damage, including neurite outgrowth and synaptic transmission. Overall, dexmedetomidine modulated the AKT/GSK-3?/CRMP-2 signaling pathway to alleviate LPS-induced neurological dysfunction.

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