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Dexmedetomidine alleviates proliferation of neural stem cells from corticosterone-induced injury and its mechanisms |
AN Yizhao1, MA Junmei1, HUANG Jianjian1, HU Zhiyan2, MEI Hongxia1, LIN Han1,2 |
1.Department of Anesthesiology, Critical Care and Pain Medicine, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China; 2.Zhejiang Province Key Lab of Anesthesiology, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, China |
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Cite this article: |
PAN Yizhao,MA Junmei,HUANG Jianjian, et al. Dexmedetomidine alleviates proliferation of neural stem cells from corticosterone-induced injury and its mechanisms[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2020, 50(2): 92-97.
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Abstract Objective: To investigate the alleviating effect of dexmedetomidine (DEX) on the proliferation of neural stem cells (NSCs) from corticosterone (CORT)-induced injury and explore the mechanisms potentially involved. Methods: NSCs were harvested from E15 SD rat brain and cultured. Neuroepithelial stem cell protein (nestin and SOX2) staining was identified. Whether NSCs express mRNA of the α-2A, α-2B, α-2C adrenoceptor subtypes was detected by Reverse transcriptase-PCR. The NSCs were randomly divided as the Control, DMSO, CORT (0.01, 0.1, 1 μmol/L), Dexmedetomidine with CORT. The NSCs in the Dexmedetomidine with CORT group were pretreated with different concentrations of dexmedetomidine (0.01, 0.1, 1 μmol/L) for 1 h prior to incubation with 1 μmol/L CORT for 24 h. Cell cytotoxicity and Edu assays were used to figure out the optimal concentration of dexmedetomidine which can be used for the protein studies; Protein levels of GSK-3β, p-GSK-3β, β-catenin and Cyclin D1 were quantified with Western blot. Results: More than 98% of them were NESTIN/SOX2 positive. The three subtypes of α-2 receptor were expressed on NSCs. There was no significant difference between each group in the release of LDH. CORT significantly decreased NSCs proliferation, however, 1 μmol/L DEX increased NSCs proliferation. CORT inhibited p-GSK-3β, β-catenin and Cyclin D1 expression compared with DMSO group, but 1 μmol/L DEX pretreatment enhanced p-GSK-3β, β-catenin, Cyclin D1 expression, compared with CORT group. Total GSK-3β levels in each group did not change significantly. The protective effect of dexmedetomidine on CORT-exposed NSCs could be partly reversed by PI3K phosphorylation inhibitor LY294002. Conclusion: Dexmedetomidine may protect NSCs from corticosterone-induced injury via the GSK-3β/β-catenin signaling pathway.
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