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

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

Wei Zeng,1,2 Chunyuan Zhang,2 Qingshan Long,3 Yalan Li1 1Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, People’s Republic of China; 2Department of Anesthesiology, Affiliated Boai Hospital of Zhongshan, Southern Medical Univers...

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Autores principales: Zeng W, Zhang C, Long Q, Li Y
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2021
Materias:
dexmedetomidine
postoperative cognitive dysfunction
neurological impairment
akt
gsk-3β
crmp-2
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Acceso en línea:https://doaj.org/article/4dac92969a2e4e40b90a9571a7b8ffeb
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spelling oai:doaj.org-article:4dac92969a2e4e40b90a9571a7b8ffeb2021-12-02T17:09:43ZDexmedetomidine Alleviates LPS-Induced Neuronal Dysfunction by Modulating the AKT/GSK-3β/CRMP-2 Pathway in Hippocampal Neurons1178-2021https://doaj.org/article/4dac92969a2e4e40b90a9571a7b8ffeb2021-03-01T00:00:00Zhttps://www.dovepress.com/dexmedetomidine-alleviates-lps-induced-neuronal-dysfunction-by-modulat-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Wei Zeng,1,2 Chunyuan Zhang,2 Qingshan Long,3 Yalan Li1 1Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, People’s Republic of China; 2Department of Anesthesiology, Affiliated Boai Hospital of Zhongshan, Southern Medical University, Zhongshan, 528400, Guangdong, People’s Republic of China; 3Department of Neurosurgery, Huizhou Third People’s Hospital, Guangzhou Medical University, Huizhou, 516002, Guangdong, People’s Republic of ChinaCorrespondence: Yalan LiDepartment of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, People’s Republic of ChinaEmail tyalan@jnu.edu.cnObjective: Dexmedetomidine, an α 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 postsynaptic 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-3β/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-3β/CRMP-2 signaling pathway to alleviate LPS-induced neurological dysfunction.Keywords: dexmedetomidine, postoperative cognitive dysfunction, neurological impairment, AKT, GSK-3β, CRMP-2Zeng WZhang CLong QLi YDove Medical Pressarticledexmedetomidinepostoperative cognitive dysfunctionneurological impairmentaktgsk-3βcrmp-2Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 671-680 (2021)
institution DOAJ
collection DOAJ
language EN
topic dexmedetomidine
postoperative cognitive dysfunction
neurological impairment
akt
gsk-3β
crmp-2
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
spellingShingle dexmedetomidine
postoperative cognitive dysfunction
neurological impairment
akt
gsk-3β
crmp-2
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Zeng W
Zhang C
Long Q
Li Y
Dexmedetomidine Alleviates LPS-Induced Neuronal Dysfunction by Modulating the AKT/GSK-3β/CRMP-2 Pathway in Hippocampal Neurons
description Wei Zeng,1,2 Chunyuan Zhang,2 Qingshan Long,3 Yalan Li1 1Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, People’s Republic of China; 2Department of Anesthesiology, Affiliated Boai Hospital of Zhongshan, Southern Medical University, Zhongshan, 528400, Guangdong, People’s Republic of China; 3Department of Neurosurgery, Huizhou Third People’s Hospital, Guangzhou Medical University, Huizhou, 516002, Guangdong, People’s Republic of ChinaCorrespondence: Yalan LiDepartment of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, People’s Republic of ChinaEmail tyalan@jnu.edu.cnObjective: Dexmedetomidine, an α 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 postsynaptic 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-3β/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-3β/CRMP-2 signaling pathway to alleviate LPS-induced neurological dysfunction.Keywords: dexmedetomidine, postoperative cognitive dysfunction, neurological impairment, AKT, GSK-3β, CRMP-2
format article
author Zeng W
Zhang C
Long Q
Li Y
author_facet Zeng W
Zhang C
Long Q
Li Y
author_sort Zeng W
title Dexmedetomidine Alleviates LPS-Induced Neuronal Dysfunction by Modulating the AKT/GSK-3β/CRMP-2 Pathway in Hippocampal Neurons
title_short Dexmedetomidine Alleviates LPS-Induced Neuronal Dysfunction by Modulating the AKT/GSK-3β/CRMP-2 Pathway in Hippocampal Neurons
title_full Dexmedetomidine Alleviates LPS-Induced Neuronal Dysfunction by Modulating the AKT/GSK-3β/CRMP-2 Pathway in Hippocampal Neurons
title_fullStr Dexmedetomidine Alleviates LPS-Induced Neuronal Dysfunction by Modulating the AKT/GSK-3β/CRMP-2 Pathway in Hippocampal Neurons
title_full_unstemmed Dexmedetomidine Alleviates LPS-Induced Neuronal Dysfunction by Modulating the AKT/GSK-3β/CRMP-2 Pathway in Hippocampal Neurons
title_sort dexmedetomidine alleviates lps-induced neuronal dysfunction by modulating the akt/gsk-3β/crmp-2 pathway in hippocampal neurons
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/4dac92969a2e4e40b90a9571a7b8ffeb
work_keys_str_mv AT zengw dexmedetomidinealleviateslpsinducedneuronaldysfunctionbymodulatingtheaktgsk3betacrmp2pathwayinhippocampalneurons
AT zhangc dexmedetomidinealleviateslpsinducedneuronaldysfunctionbymodulatingtheaktgsk3betacrmp2pathwayinhippocampalneurons
AT longq dexmedetomidinealleviateslpsinducedneuronaldysfunctionbymodulatingtheaktgsk3betacrmp2pathwayinhippocampalneurons
AT liy dexmedetomidinealleviateslpsinducedneuronaldysfunctionbymodulatingtheaktgsk3betacrmp2pathwayinhippocampalneurons
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